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    <head><title>Glycemia, starch, and sugar in context</title></head>
    <body>
        <h1>
            Glycemia, starch, and sugar in context
        </h1>

        <p>
            <hr />
            <hr />
        </p>

        <p>
            <strong><em>Monosaccharide -- a simple sugar; examples, glucose,</em></strong>
            <em> </em>
            <strong><em>fructose, ribose, galactose (galactose is also called cerebrose, brain sugar).</em></strong>
        </p>
        <p>
            <strong><em>Disaccharide -- two monosaccharides bound together; examples, sucrose, lactose, maltose.</em
                ></strong>
        </p>
        <p>
            <strong><em>Oligosaccharide -- a short chain of monosaccharides, including disaccharides and slightly longer
                    chains.</em></strong>
        </p>
        <p><strong><em>Polysaccharide -- example, starch, cellulose, glycogen.</em></strong></p>
        <p><strong><em>Glycation -- the attachment of a sugar to a protein.</em></strong></p>

        <p>
            <strong><em>Lipolysis - the liberation of free fatty acids from triglycerides, the neutral form in which
                    fats are stored, bound to glycerine.</em></strong>
        </p>
        <p>
            <hr />
            <hr />
        </p>
        <p>
            In the 1920s, "diabetes" was thought to be a disease of insulin deficiency. Eventually, measurements of
            insulin showed that "diabetics" often had normal amounts of insulin, or above-normal amounts. There are now
            "two kinds of diabetes," with suggestions that "the disease" will soon be further subdivided.
        </p>
        <p>
            The degenerative diseases that are associated with hyperglycemia and commonly called diabetes, are only
            indirectly related to insulin, and as an approach to understanding or treating diabetes, the "glycemic
            index" of foods is useless. Physiologically, it has no constructive use, and very little meaning.
        </p>
        <p>
            Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of
            the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the
            "insulin-like activity" of the blood, with potassium being probably the largest factor. There probably isn't
            any process in the body that doesn't potentially affect blood sugar.
        </p>

        <p>
            Glucagon, cortisol, adrenalin, growth hormone and thyroid tend to increase the blood sugar, but it is common
            to interpret hyperglycemia as "diabetes," without measuring any of these factors. Even when "insulin
            dependent diabetes" is diagnosed, it isn't customary to measure the insulin to see whether it is actually
            deficient, before writing a prescription for insulin. People resign themselves to a lifetime of insulin
            injections, without knowing why their blood sugar is high.
        </p>
        <p>
            Insulin release is also stimulated by amino acids such as leucine, and insulin stimulates cells to absorb
            amino acids and to synthesize proteins. Since insulin lowers blood sugar as it disposes of amino acids,
            eating a large amount of protein without carbohydrate can cause a sharp decrease in blood sugar. This leads
            to the release of adrenalin and cortisol, which raise the blood sugar. Adrenalin causes fatty acids to be
            drawn into the blood from fat stores, especially if the liver's glycogen stores are depleted, and cortisol
            causes tissue protein to be broken down into amino acids, some of which are used in place of carbohydrate.
            Unsaturated fatty acids, adrenaline, and cortisol cause insulin resistance.
        </p>
        <p>
            <hr />
            <hr />
        </p>
        <p>
            "Professional opinion" can be propagated about 10,000 times faster than research can evaluate it, or, as C.
            H. Spurgeon said, "A lie travels round the world while Truth is putting on her boots."
        </p>
        <p>
            In the 1970s, dietitians began talking about the value of including "complex carbohydrates" in the diet.
            Many dietitians (all but one of the Registered Dietitians that I knew of) claimed that starches were more
            slowly absorbed than sugars, and so should be less disruptive to the blood sugar and insulin levels. People
            were told to eat whole grains and legumes, and to avoid fruit juices.
        </p>
        <p>
            These recommendations, and their supporting ideology, are still rampant in the culture of the United States,
            fostered by the U.S. Department of Agriculture and the American Dietetic Association and the American
            Diabetes Association and innumerable university departments of home economics, dietetics, or nutrition.
        </p>
        <p>
            Judging by present and past statements of the American Dietetic Association, I think some kind of
            institutional brain defect might account for their recommendations. Although the dietetic association now
            feebly acknowledges that sugars don't raise the blood sugar more quickly than starches do, they can't get
            away from their absurd old recommendations, which were never scientifically justified<strong>:</strong> "Eat
            more starches, such as bread, cereal, and starchy vegetables--6 servings a day or more. Start the day with
            cold (dry) cereal with nonfat/skim milk or a bagel with one teaspoon of jelly/jam. Put starch center
            stage--pasta with tomato sauce, baked potato with chili, rice and stir-fried beef and vegetables. Add cooked
            black beans, corn, or garbanzo beans (chickpeas) to salads or casseroles."
        </p>

        <p>
            The Dietetic Association's association with General Mills, the breakfast cereal empire, (and Kellog,
            Nabisco, and many other food industry giants) might have something to do with their starchy opinions.
            Starch-grain embolisms can cause brain damage, but major money can also make people say stupid things.
        </p>
        <p>
            In an old experiment, a rat was tube-fed ten grams of corn-starch paste, and then anesthetized. Ten minutes
            after the massive tube feeding, the professor told the students to find how far the starch had moved along
            the alimentary canal. No trace of the white paste could be found, demonstrating the speed with which starch
            can be digested and absorbed. The very rapid rise of blood sugar stimulates massive release of insulin, and
            rapidly converts much of the carbohydrate into fat.
        </p>
        <p>
            It was this sort of experiment that led to the concept of "glycemic index," that ranks foods according to
            their ability to raise the blood sugar. David Jenkins, in 1981, knew enough about the old studies of starch
            digestion to realize that the dietitians had created a dangerous cult around the "complex carbohydrates,"
            and he did a series of measurements that showed that starch is more "glycemic" than sucrose. But he simply
            used the amount of increase in blood glucose during the first two hours after ingesting the food sample,
            compared to that following ingestion of pure glucose, for the comparison, neglecting the physiologically
            complex facts, all of the processes involved in causing a certain amount of glucose to be present in the
            blood during a certain time. (Even the taste of sweetness, without swallowing anything, can stimulate the
            release of glucagon, which raises blood sugar.)
        </p>
        <p>
            More important than the physiological vacuity of a simple glycemic measurement was the ideology within which
            the whole issue developed, namely, the idea that diabetes (conceived as chronic hyperglycemia) is caused by
            eating too much sugar, i.e., chronic hyperglycemia the illness is caused by the recurrent hyperglycemia of
            sugar gluttony. The experiments of Bernardo Houssay (1947 Nobel laureate) in the 1940s, in which sugar and
            coconut oil protected against diabetes, followed by Randle's demonstration of the antagonism between fats
            and glucose assimilation, and the growing recognition that polyunsaturated fatty acids cause insulin
            resistance and damage the pancreas, have made it clear that the dietetic obsession with sugar in relation to
            diabetes has been a dangerous diversion that has retarded the understanding of degenerative metabolic
            diseases.
        </p>

        <p>
            Starting with the insulin industry, a culture of diabetes and sugar has been fabulized and expanded and
            modified as new commercial industries found ways to profit from it. Seed oils, fish oils, breakfast cereals,
            soybean products, and other things that were never eaten by any animal in millions of years of evolution
            have become commonplace as "foods," even as "health foods."
        </p>
        <p>
            Although many things condition the rate at which blood sugar rises after eating carbohydrates, and affect
            the way in which blood glucose is metabolized, making the idea of a "glycemic index" highly misleading, it
            is true that blood sugar and insulin responses to different foods have some meaningful effects on physiology
            and health.
        </p>
        <p>
            Starch and glucose efficiently stimulate insulin secretion, and that accelerates the disposition of glucose,
            activating its conversion to glycogen and fat, as well as its oxidation. <strong>Fructose inhibits the
                stimulation of insulin by glucose, so this means that eating ordinary sugar, sucrose (a disaccharide,
                consisting of glucose and fructose), in place of starch, will reduce the tendency to store fat.</strong>
            Eating "complex carbohydrates," rather than sugars, is a reasonable way to promote obesity. Eating starch,
            by increasing insulin and lowering the blood sugar, stimulates the appetite, causing a person to eat more,
            so the effect on fat production becomes much larger than when equal amounts of sugar and starch are eaten.
            The obesity itself then becomes an additional physiological factor; the fat cells create something analogous
            to an inflammatory state. There isn't anything wrong with a high carbohydrate diet, and even a high starch
            diet isn't necessarily incompatible with good health, but when better foods are available they should be
            used instead of starches. For example, fruits have many advantages over grains, besides the difference
            between sugar and starch. Bread and pasta consumption are strongly associated with the occurrence of
            diabetes, fruit consumption has a strong inverse association.
        </p>
        <p>
            Although pure fructose and sucrose produce less glycemia than glucose and starch do, the different effects
            of fruits and grains on the health can't be reduced to their effects on blood sugar.
        </p>

        <p>
            Orange juice and sucrose have a lower glycemic index than starch or whole wheat or white bread, but it is
            common for dietitians to argue against the use of orange juice, because its index is the same as that of
            Coca Cola. But, if the glycemic index is very important, to be rational they would have to argue that Coke
            or orange juice should be substituted for white bread.
        </p>
        <p>
            After decades of "education" to promote eating starchy foods, obesity is a bigger problem than ever, and
            more people are dying of diabetes than previously. The age-specific incidence of most cancers is increasing,
            too, and there is evidence that starch, such as pasta, contributes to breast cancer, and possibly other
            types of cancer.
        </p>
        <p>
            The epidemiology would appear to suggest that complex carbohydrates cause diabetes, heart disease, and
            cancer. If the glycemic index is viewed in terms of the theory that hyperglycemia, by way of
            "glucotoxicity," causes the destruction of proteins by glycation, which is seen in diabetes and old age,
            that might seem simple and obvious.
        </p>

        <a name="0.1_table04"></a>

        <a name="0.1_table03"></a>

        <a name="0.1_table02"></a>

        <a name="0.1_table01"></a>

        <p>
            But there are many reasons to question that theory.
        </p>
        <p>
            Oxidation of sugar is metabolically efficient in many ways, including sparing oxygen consumption. It
            produces more carbon dioxide than oxidizing fat does, and carbon dioxide has many protective functions,
            including increasing Krebs cycle activity and inhibiting toxic damage to proteins. The glycation of proteins
            occurs under stress, when less carbon dioxide is being produced, and the proteins are normally protected by
            carbon dioxide.
        </p>
        <p>
            When sugar (or starch) is turned into fat, the fats will be either saturated, or in the series derived from
            omega -9 monounsaturated fatty acids. When sugar isn't available in the diet, stored glycogen will provide
            some glucose (usually for a few hours, up to a day), but as that is depleted, protein will be metabolized to
            provide sugar. If protein is eaten without carbohydrate, it will stimulate insulin secretion, lowering blood
            sugar and activating the stress response, leading to the secretion of adrenalin, cortisol, growth hormone,
            prolactin, and other hormones. The adrenalin will mobilize glycogen from the liver, and (along with other
            hormones) will mobilize fatty acids, mainly from fat cells. Cortisol will activate the conversion of protein
            to amino acids, and then to fat and sugar, for use as energy. (If the diet doesn't contain enough protein to
            maintain the essential organs, especially the heart, lungs, and brain, they are supplied with protein from
            the skeletal muscles. Because of the amino acid composition of the muscle proteins, their destruction
            stimulates the formation of additional cortisol, to accelerate the movement of amino acids from the less
            important tissues to the essential ones.)
        </p>

        <p>
            The diabetic condition is similar in many ways to stress, inflammation, and aging, for example in the
            chronic elevation of free fatty acids, and in various mediators of inflammation, such as tumor necrosis
            factor (TNF).
        </p>
        <p>
            Rather than the sustained hyperglycemia which is measured for determining the glycemic index, I think the
            "diabetogenic" or "carcinogenic" action of starch has to do with the stress reaction that follows the
            intense stimulation of insulin release. This is most easily seen after a large amount of protein is eaten.
            Insulin is secreted in response to the amino acids, and besides stimulating cells to take up the amino acids
            and convert them into protein, the insulin also lowers the blood sugar. This decrease in blood sugar
            stimulates the formation of many hormones, including cortisol, and under the influence of cortisol both
            sugar and fat are produced by the breakdown of proteins, including those already forming the tissues of the
            body. At the same time, adrenalin and several other hormones are causing free fatty acids to appear in the
            blood.
        </p>
        <p>
            Since the work of Cushing and Houssay, it has been understood that blood sugar is controlled by antagonistic
            hormones<strong>:</strong> Remove the pituitary along with the pancreas, and the lack of insulin doesn't
            cause hyperglycemia. If something increases cortisol a little, the body can maintain normal blood sugar by
            secreting more insulin, but that tends to increase cortisol production. A certain degree of glycemia is
            produced by a particular balance between opposing hormones.
        </p>
        <p>
            Tryptophan, from dietary protein or from the catabolism of muscles, is turned into serotonin which activates
            the pituitary stress hormones, increasing cortisol, and intensifying catabolism, which releases more
            tryptophan. It suppresses thyroid function, which leads to an increased need for the stress hormones.
            Serotonin impairs glucose oxidation, and contributes to many of the problems associated with diabetes.
        </p>
        <p>
            "Diabetes" is often the diagnosis, when excess cortisol is the problem. The hormones have traditionally not
            been measured before diagnosing diabetes and prescribing insulin or other chemical to lower the blood sugar.
            Some of the worst effects of "diabetes," including retinal damage, are caused or exacerbated by insulin
            itself.
        </p>

        <p>
            Antiserotonin drugs can sometimes alleviate stress and normalize blood sugar. Simply eating sucrose was
            recently discovered to restrain the stress hormone system ("A new perspective on glucocorticoid
            feedback<strong>:</strong> relation to stress, carbohydrate feeding and feeling better," J Neuroendocrinol
            13(9), 2001, KD Laugero).
        </p>
        <p>
            The free fatty acids released by the stress hormones serve as supplemental fuel, and increase the
            consumption of oxygen and the production of heat. (This increased oxygen demand is a problem for the heart
            when it is forced to oxidize fatty acids. [A. Grynberg, 2001]) But if the stored fats happen to be
            polyunsaturated, they damage the blood vessels and the mitochondria, suppress thyroid function, and cause
            "glycation" of proteins. They also damage the pancreas, and impair insulin secretion.
        </p>
        <p>
            A repeated small stress, or overstimulation of insulin secretion, gradually tends to become amplified by the
            effects of tryptophan and the polyunsaturated fatty acids, with these fats increasing the formation of
            serotonin, and serotonin increasing the liberation of the fats.
        </p>
        <p>
            The name, "glycation," indicates the addition of sugar groups to proteins, such as occurs in diabetes and
            old age, but when tested in a controlled experiment, <strong>lipid peroxidation of polyunsaturated fatty
                acids produces the protein damage about 23 times faster than the simple sugars do</strong>
            (Fu, et al., 1996). And the oxidation of fats rather than glucose means that the proteins won't have as much
            protective carbon dioxide combined with their reactive nitrogen atoms, so the real difference in the
            organism is likely to be greater than that seen by Fu, et al.
        </p>

        <p>
            These products of lipid peroxidation, HNE, MDA, acrolein, glyoxal, and other highly reactive aldehydes,
            damage the mitochondria, reducing the ability to oxidize sugar, and to produce energy and protective carbon
            dioxide.
        </p>
        <p>
            <strong>Fish oil, which is extremely unstable in the presence of oxygen and metals such as iron, produces
                some of these dangerous products very rapidly.</strong>
            The polyunsaturated "essential fatty acids" and their products, arachidonic acid and many of the
            prostaglandin-like materials, also produce them.
        </p>
        <p>
            When glucose can't be oxidized, for any reason, there is a stress reaction, that mobiles free fatty acids.
            Drugs that oppose the hormones (such as adrenalin or growth hormone) that liberate free fatty acids have
            been used to treat diabetes, because lowering free fatty acids can restore glucose oxidation.
        </p>
        <p>
            Brief exposures to polyunsaturated fatty acids can damage the insulin-secreting cells of the pancreas, and
            the mitochondria in which oxidative energy production takes place. Prolonged exposure causes progressive
            damage. Acutely, the free polyunsaturated fatty acids cause capillary permeability to increase, and this can
            be detected at the beginning of "insulin resistance" or "diabetes." After chronic exposure, the leakiness
            increases and albumin occurs in the urine, as proteins leak out of the blood vessels. The retina and brain
            and other organs are damaged by the leaking capillaries.
        </p>
        <p>
            The blood vessels and other tissues are also damaged by the chronically increased cortisol, and at least in
            some tissues (the immune system is most sensitive to the interaction) the polyunsaturated fats increase the
            ability of cortisol to kill the cells.
        </p>

        <p>
            When cells are stressed, they are likely to waste glucose in two ways, turning some of it into lactic acid,
            and turning some into fatty acids, even while fats are being oxidized, in place of the sugar that is
            available. Growth hormone and adrenalin, the stress-induced hormones, stimulate the oxidation of fatty
            acids, as well as their liberation from storage, so the correction of energy metabolism requires the
            minimization of the stress hormones, and of the free fatty acids. Prolactin, ACTH, and estrogen also cause
            the shift of metabolism toward the fatty acids.
        </p>
        <p>
            Sugar and thyroid hormone (T3, triiodothyronine) correct many parts of the problem. The conversion of T4
            into the active T3 requires glucose, and in diabetes, cells are deprived of glucose. Logically, all
            diabetics would be functionally hypothyroid. Providing T3 and sugar tends to shift energy metabolism away
            from the oxidation of fats, back to the oxidation of sugar.
        </p>
        <p>
            Niacinamide, used in moderate doses, can safely help to restrain the excessive production of free fatty
            acids, and also helps to limit the wasteful conversion of glucose into fat. There is evidence that diabetics
            are chronically deficient in niacin. Excess fatty acids in the blood probably divert tryptophan from niacin
            synthesis into serotonin synthesis.
        </p>
        <p>
            Sodium, which is lost in hypothyroidism and diabetes, increases cellular energy. Diuretics, that cause loss
            of sodium, can cause apparent diabetes, with increased glucose and fats in the blood. <strong>Thyroid,
                sodium, and glucose work very closely together to maintain cellular energy and stability.</strong>
        </p>
        <p>
            In Houssay's experiments, sugar, protein, and coconut oil protected mice against developing diabetes. The
            saturated fats of coconut oil are similar to those we synthesize ourselves from sugar. Saturated fats, and
            the polyunsaturated fats synthesized by plants, have very different effects on many important physiological
            processes. In every case I know about, the vegetable polyunsaturated fats have harmful effects on our
            physiology.
        </p>

        <p>
            For example, they bind to the "receptor" proteins for cortisol, progesterone, and estrogen, and to all of
            the major proteins related to thyroid function, and to the vesicles that take up nerve transmitter
            substances, such as glutamic acid.
        </p>
        <p>
            They allow glutamic acid to injure and kill cells through excessive stimulation; this process is similar to
            the nerve damage done by cobra venom, and other toxins.
        </p>
        <p>
            Excess cortisol makes nerve cells more sensitive to excitotoxicity, but the cells are protected if they are
            provided with an unusually large amount of glucose.
        </p>
        <p>
            The cells of the thymus gland are very sensitive to damage by stress or cortisol, but they too can be
            rescued by giving them enough extra glucose to compensate for the cortisol. Polyunsaturated fatty acids have
            the opposite effect, sensitizing the thymus cells to cortisol. This partly accounts for the
            immunosuppressive effects of the polyunsaturated fats. (AIDS patients have increased cortisol and
            polyunsaturated fatty acids in their blood.[E.A. Nunez, 1988.])
        </p>
        <p>
            Unsaturated fatty acids activate the stress hormones, sugar restrains them.
        </p>
        <p>
            Simply making animals "deficient" in the unsaturated vegetable oils (which allows them to synthesize their
            own series of animal polyunsaturated fats, which are very stable), protects them against "autoimmune"
            diabetes, and against a variety of other "immunological" challenges. The "essential fatty acid" deficiency
            increases the oxidation of glucose, as it increases the metabolic rate generally.
        </p>

        <p>
            Saturated fats improve the insulin-secreting response to glucose.
        </p>
        <p>
            The protective effects of sugar, and the harmful effects of excessive fat metabolism, are now being widely
            recognized, in every field of physiology. The unsaturated vegetable fats, linoleic and linolenic acid and
            their derivatives, such as arachidonic acid and the long chain fish oils, have excitatory, stress promoting
            effects, that shift metabolism away from the oxidation of glucose, and finally destroy the respiratory
            metabolism altogether. Since cell injury and death generally involve an imbalance between excitation and the
            ability to produce energy, it is significant that the oxidation of unsaturated fatty acids seems to consume
            energy, lowering cellular ATP (Clejan, et al, 1986).
        </p>
        <p>
            The bulk of the age-related tissue damage classified as "glycation end-products" (or "advanced glycation
            end-products," AGE) is produced by decomposition of the polyunsaturated fats, rather than by sugars, and
            this would be minimized by the protective oxidation of glucose to carbon dioxide.
        </p>
        <p>
            Protein of the right kind, in the right amount, is essential for reducing stress. Gelatin, with its
            antiinflammatory amino acid balance, helps to regulate fat metabolism.
        </p>
        <p>
            Aspirin's antiinflammatory actions are generally important when the polyunsaturated fats are producing
            inflammatory and degenerative changes, and aspirin prevents many of the problems associated with diabetes,
            reducing vascular leakiness. It improves mitochondrial respiration (De Cristobal, et al., 2002) and helps to
            regulate blood sugar and lipids (Yuan, et al., 2001). Aspirin's broad range of beneficial effects is
            probably analogous to vitamin E's, being proportional to protection against the broad range of toxic effects
            of the polyunsaturated "essential" fatty acids.
        </p>
        <p>
            <strong><h3>REFERENCES</h3></strong>
        </p>
        <p>
            <strong>Diabetes Care 1993 Sep;16(9):1301-5. Metabolic effects of dietary sucrose in type II diabetic
                subjects. Bantle JP, Swanson JE, Thomas W, Laine DC "CONCLUSIONS--A high sucrose diet did not adversely
                affect glycemia or lipemia in type II diabetic subjects."</strong>
        </p>
        <p>
            Am J Physiol 1997 Nov;273(5 Pt 1):C1732-8. <strong>Glycolysis inhibition by palmitate in renal cells
                cultured in a two-chamber system.</strong> Bolon C, Gauthier C, Simonnet H ""palmitate promoted a
            long-term decrease in lactate production and sustained excellent cellular growth. After 4 days of contact,
            decreased glycolysis was maintained even in the absence of carnitine"."
        </p>
        <p>
            Diabetes 1989 Oct;38(10):1314-9. <strong>Effects of fish oil supplementation on glucose and lipid metabolism
                in NIDDM.</strong> Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN.
            Garvan "<strong>In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM
                subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil
                supplementation was not significantly different from fish oil,
            </strong>suggesting that the negative effects on glucose metabolism may be related to the extra energy or
            fat intake." Randomized Controlled Trial
        </p>

        <p>
            Ann Clin Lab Sci 1988 Jul-Aug;18(4):337-43. <strong>Effects of peroxidized polyunsaturated fatty acids on
                mitochondrial function and structure: pathogenetic implications for Reye's syndrome.</strong> Brown RE,
            Bhuvaneswaran C, Brewster M. "<strong>Linoleic acid, a polyunsaturated fatty acid, is a constituent of
                margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased
                concentrations of polyunsaturated fatty acids have been found in sera from patients with RS." Isolated
                rat liver mitochondria exposed to the</strong> peroxidized (but not unperoxidized) methyl esters of
            linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and
            in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated
            spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and
            was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of
            RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide
            concentration in the medium."
        </p>
        <p>
            J Neurochem 1982 Feb;38(2):525-31.<strong>
                Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices.
            </strong>
            Chan PH, Yurko M, Fishman RA. "<strong>These data suggest that lipases are activated by free radicals and
                lipid peroxides in the pathogenesis of cellular swelling."</strong>
        </p>

        <p>
            J Neurochem 1988 Apr;50(4):1185-93. <strong>Induction of intracellular superoxide radical formation by
                arachidonic acid and by polyunsaturated fatty acids in primary astrocytic cultures.</strong> Chan PH,
            Chen SF, Yu AC. "Other PUFAs, including linoleic acid, linolenic acid, and docosahexaenoic acid, were also
            effective in stimulating NBF formation in astrocytes, whereas saturated palmitic acid and monounsaturated
            oleic acid were ineffective. Similar effects of these PUFAs were observed in malondialdehyde formation in
            cells and lactic acid accumulation in incubation medium. These data indicate that both membrane integrity
            and cellular metabolism were perturbed by arachidonic acid and by other PUFAs."
        </p>
        <p>
            Can J Biochem 1978 Feb;56(2):111-6. <strong>Uncoupling activity of endogenous free fatty acids in rat liver
                mitochondria.</strong> Chan SH, Higgins E Jr.
        </p>
        <p>
            J Neurochem 1980 Oct;35(4):1004-7. <strong>Transient formation of superoxide radicals in polyunsaturated
                fatty acid-induced brain swelling.
            </strong>
            Chan PH, Fishman RA. "The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3),
            arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in
            superoxide and membrane lipid<strong>
                peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect."</strong> "These in vitro
            data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the
            mechanism of polyunsaturated fatty acid-induced brain edema."
        </p>

        <p>
            Arch Biochem Biophys 1986 May 1;246(2):820-8. <strong>Effect of growth hormone on fatty acid oxidation:
                growth hormone increases the activity of 2,4-dienoyl-CoA reductase in mitochondria.
            </strong>Clejan S, Schulz H. "<strong>Rates of respiration supported by polyunsaturated fatty
                acylcarnitines, in contrast to rates observed with palmitoylcarnitine or oleoylcarnitine, were slightly
                lower in hypophysectomized rats than in normal rats, but were higher in hypophysectomized rats treated
                with growth hormone. The effects were most pronounced with docosahexaenoylcarnitine, the substrate with
                the highest degree of unsaturation.</strong>
            Since uncoupling of mitochondria with 2,4-dinitrophenol resulted in lower rates of
            docosahexaenoylcarnitine-supported respiration, while substitution of ATP for ADP yielded higher rates, it
            appears that <strong>
                energy is required for the effective oxidation of polyunsaturated</strong>
            fatty acids. Growth hormone treatment of hypophysectomized rats caused a threefold increase in t`he activity
            of 2,4-dienoyl-CoA reductase or 4-enoyl-CoA reductase (EC 1.3.1.34) in mitochondria, but not in
            peroxisomes." "Rates of acetoacetate formation from linolenoylcarnitine, but not from palmitoylcarnitine,
            were stimulated by glutamate in mitochondria from hypophysectomized rats and hypophysectomized rats treated
            with growth hormone. All data together <strong>lead to the conclusion that the mitochondrial oxidation of
                highly polyunsaturated fatty acids is limited by the availability of NADPH
            </strong>and the activity of 2,4-dienoyl-CoA reductase which is induced by growth hormone treatment."
        </p>
        <p>
            V. Coiro, et al., "Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with
            or without neuropathy," Metabolism--Clinical and Experimental 44(4), 538-542, 1995.<strong>
                "...basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal
                controls." "...even uncomplicated diabetes mellitus is associated with adrenal hyperfunction."</strong>
        </p>
        <p>
            Stroke 2002 Jan;33(1):261-7. <strong>
                Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of
                aspirin in rat cortical neurons exposed to oxygen-glucose deprivation.</strong> De Cristobal J, Cardenas
            A, Lizasoain I, Leza JC, Fernandez-Tome P, Lorenzo P, Moro MA. "Aspirin is preventive against stroke not
            only because of its antithrombotic properties but also by other direct effects." "Aspirin inhibited
            OGD-induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition
            of the transcription factor nuclear factor-kappaB (which are &gt;1 mmol/L), an effect that <strong
            >correlated with the inhibition caused by aspirin on glutamate release.</strong> This effect was shared by
            sodium salicylate but not by indomethacin, thus excluding the involvement of cyclooxygenase. A
            pharmacological dissection of the components involved indicated that aspirin selectively inhibits the
            increase in extracellular glutamate concentration that results from reversal of the glutamate transporter, a
            component of release that is due to ATP depletion. Moreover, aspirin-afforded neuroprotection occurred in
            parallel with a lesser decrease in ATP levels after OGD. <strong>Aspirin elevated ATP levels not only in
                intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase
                in NADH-dependent respiration by brain submitochondrial particles."</strong> "Taken together, our
            present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at
            concentrations in the antithrombotic-analgesic range, useful in the management of patients with high risk of
            ischemic events."
        </p>

        <p>
            Diabetes 2002 Jun;51(6):1825-33. <strong>The composition of dietary fat directly influences
                glucose-stimulated insulin secretion in rats.</strong> Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y,
            Uchino H, Giacca A, McGarry JD. <strong>"Insulin responses during hyperglycemic clamps were augmented by
                saturated but not unsaturated fat (580 +/- 25, 325 +/- 30, and 380 +/- 50 pmol x l(-1) x min(-1) in
                Lard, Soy, and Low-Fat groups, respectively).</strong>" <strong>
                "These data indicate that prolonged exposure to saturated fat enhances GSIS (but this does not entirely
                compensate for insulin resistance), whereas unsaturated fat, given in the diet or by infusion, impairs
                GSIS."</strong>
        </p>
        <p>
            C. Douillet and M. Ciavatti, <strong>"Effect of vitamin E treatment on tissue fatty acids and cholesterol
                content in experimental diabetes,"</strong>
            J. Nutr. Biochem. 6(6), 319-326, 1995. <strong>
                "Diabetes induced a decrease of monounsaturated fatty acids and particularly palmitoleic acid in all
                studied tissues: liver, aorta, plasma." "C18:3 n-6 and C20:4 n-6 were increased by diabetes."</strong>
        </p>

        <p>
            Diabetologia 1992 Feb;35(2):165-72. <strong>Long-term effects of linoleic-acid-enriched diet on albuminuria
                and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin
                excretion.</strong> Dullaart RP, Beusekamp BJ, Meijer S, Hoogenberg K, van Doormaal JJ, Sluiter WJ. "We
            conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet
            on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary
            albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min)." "Clinical
            characteristics,<strong> </strong>
            albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were
            similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/-
            4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/-
            0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95%
            confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval,
            11 to 127) (p less than 0.01) during the second year."
        </p>
        <p>
            J Biol Chem 1996 Apr 26;271(17):9982-6. <strong>The advanced glycation end product,
                Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation
                reactions.</strong>
            Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. Nepsilon-(Carboxymethyl)lysine (CML) is an
            advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation
            (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of
            polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML
            content of low density lipoprotein increased in concert with conjugated dienes but was independent of the
            presence<strong>
                of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner
                in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate;
                only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase
                from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for
                protein incubated under the same conditions with glucose.</strong> Glyoxal, a known precursor of CML,
            was also formed during incubation of Rnase with arachidonate. These results suggest that lipid peroxidation,
            as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a
            general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.
        </p>

        <p>
            J Nutr 2000 Oct;130(10):2503-7. <strong>A high carbohydrate versus a high monounsaturated fatty acid diet
                lowers the atherogenic potential of big VLDL particles in patients with type 1 diabetes.</strong>
            Georgopoulos A, Bantle JP, Noutsou M, Hoover HA. "A high (25%) monounsaturated fatty acid (Mono) diet and a
            high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19
            normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein,
            polyunsaturated/saturated fatty acids, cholesterol and fiber content." "We conclude that a high CHO diet
            might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could
            increase the atherosclerotic risk in patients with diabetes."
        </p>
        <p>
            J. Girard, "Role of free fatty acids in insulin resistance of subjects with non-insulin-dependent diabetes,"
            Diabetes Metab. 21(2), 79-88, 1995. <strong>"Studies performed in the rat suggest that impaired
                glucose-induced insulin secretion could also be related to chronic exposure of pancreatic beta cells to
                elevated plasma free fatty acid levels."</strong>
        </p>
        <p>
            Ann Intern Med 1988 May;108(5):663-8. <strong>Adverse metabolic effect of omega-3 fatty acids in
                non-insulin-dependent diabetes mellitus.
            </strong>
            <hr />
            <strong><hr /></strong> but unchanged glucose disposal rates. Caution should be used when recommending
            omega-3 fatty acids in type II diabetic persons."
        </p>
        <p>
            A. Golay, et al., "Effect of lipid oxidation on the regulation of glucose utilization in obese patients,"
            Acta Diabetologica 32(1), 44-48, 1995. <strong>[Free fatty acids strongly and quickly depress the ability to
                oxidize or store glucose.]</strong>
        </p>
        <p>
            Biol Neonate 1985;47(6):343-9. <strong>Increased maternal-fetal transport of fat in diabetes assessed by
                polyunsaturated fatty acid content in fetal lipids.</strong>
            Goldstein R, Levy E, Shafrir E. The distribution of fatty acids was determined by gas-liquid chromatography
            in total lipid and triglyceride fraction of extracts of several tissues of streptozotocin-diabetic rats and
            their fetuses on day 20 of pregnancy. In maternal rats, diabetes did not significantly affect fatty acid
            distribution apart from small changes in the relative content of linoleate in adipose tissue and liver. In
            the placenta, the fetal carcass and the fetal liver the<strong>
                triglyceride content increased approximately 2-fold as a result of maternal diabetes, in association
                with the elevation in triglycerides and free fatty</strong>

            acids in the maternal circulation. A pronounced increase in the relative content<strong>
                of linoleate was recorded in the total lipid and triglyceride extracts of placenta (35 and 59%), fetal
                carcass (56 and 66%) and fetal liver (100 and 205%). Small increases in arachidonate proportion were
                also seen in some fetal tissues. The large increase in fetal hepatic linoleate indicates that
                this</strong> tissue is an important uptake target of maternal lipids transported in excess into the
            fetus. The results confirm the previous observations on increased transplacental fat passage in diabetes by
            demonstrating that the increment in the essential fatty acid, linoleate, parallels the diabetes-induced
            triglyceride accumulation in the fetoplacental unit.
        </p>
        <p>
            A. Gomes, et al., "Anti-hyperglycemic effect of black tea (Camellia sinensis) in rat," J. of
            Ethnopharmacology 45(3), 223-226, 1995. <strong>
                It "was found to possess both preventive and curative effects on experimentally produced diabetes in
                rats."</strong>
        </p>
        <p>
            J Endocrinol 2002 Apr;173(1):73-80. <strong>Acute effects of fatty acids on insulin secretion from rat and
                human islets of Langerhans.</strong> Gravena C, Mathias PC, Ashcroft SJ. "Long-chain fatty<strong>
                acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids
                (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate)."</strong
            >
        </p>

        <p>
            Diabetes Metab 2001 Nov;27(5 Pt 2):S12-9. <strong>[Modifications in myocardial energy metabolism in diabetic
                patients]]</strong> [Article in French] Grynberg A. "<strong>Because FA is the main heart fuel (although
                the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a
                balanced fatty acid (FA) metabolism.</strong> Several pathological situations are associated with an
            accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is
            characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new
            strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP
            production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA
            uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell." "Sudden death,
            hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in
            cardiac membranes."
        </p>
        <p>
            Diabetologia 1996 Mar;39(3):251-5. <strong>Acceleration of experimental diabetic retinopathy in the rat by
                omega-3 fatty Acids.</strong> Hammes HP, Weiss A, Fuhrer D, Kramer HJ, Papavassilis C, Grimminger F.
            Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic
            retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production,
            increased blood viscosity in association with impaired cell deformability and pathologic
            leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg
            Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could
            inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of
            fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty
            acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest
            preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries.
            Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty
            acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic
            rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the
            formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group
            (115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We
            conclude from this study that dietary fish oil supplementation may be harmful for the diabetic
            microvasculature in the retina.
        </p>
        <p>
            Y. Hattori, et al., "Phorbol esters elicit Ca++-dependent delayed contractions in diabetic rat aorta," Eur.
            J. Pharmacol. 279(1), 51-58, 1995. <strong>[Diabetic tissue is more responsive to activation of protein
                kinase C by phorbol esters.]</strong>
        </p>

        <p>
            Nutr Metab 1975;18(1):41-8. <strong>Adipose tissue metabolism in essential fatty acid deficienty. Effects of
                prostaglandin e1, epinephrine, and ACTH.</strong>
            Hazinski TA, Barr M, Hertelendy F. In an effort to better define some of the metabolic changes that
            accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD
            and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and
            ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or
            6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and
            glyceride-glycerol was determined. <strong>It was found that EFAD increased glucose uptake over controls
                which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of
                the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls.
                ACTH1-18</strong> (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups,
            respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups,
            respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the
            inhibitory action of the catecholamine in both groups."
        </p>
        <p>
            J Neurosci Res 1989 Oct;24(2):247-50. <strong>Brain mitochondrial swelling induced by arachidonic acid and
                other long chain free fatty acids.</strong> Hillered L, Chan PH. "<strong>Polyunsaturated fatty acids
                (PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while
                monounsaturated and saturated long chain fatty acids do not possess this quality."</strong>
            "<strong>ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of
                bovine serum albumin could only prevent but not reverse the swelling." "Moreover, reversal of the
                swelling occurred without recovery of respiratory function."
            </strong>
        </p>

        <p>
            J Neurosci Res 1988 Aug;20(4):451-6. <strong>
                Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia.
            </strong>
            Hillered L, Chan PH.
        </p>
        <p>
            B. A. Houssay and C. Martinez, <strong>"Experimental diabetes and diet,"</strong>
            Science 105, 548-549, 1947. <strong>[Mortality was zero on the high coconut oil diet, 100% on the high lard
                diet. It was 90% on the low protein diet, and 33% on the high protein diet. With a combination of
                coconut oil and lard, 20%.]</strong>
        </p>
        <p>
            B. A. Houssay, et al., <strong>"Accion de la administracion prolongada de glucosa sobre la diabetes de la
                rata,"</strong> Rev. Soc. argent. de biol. 23, 288-293, 1947.
        </p>

        <p>
            S. Ikemoto, et al., <strong>"High fat diet-induced hyperglycemia: Prevention by low level expression of a
                glucose transporter (GLUT4) minigene in transgenic mice,"</strong> Proc. Nat. Acad. Sci. USA 92(8),
            3096-3099, 1995. <strong>
                "...mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and
                obesity."</strong>
        </p>
        <p>
            M. Inaba, et al., <strong>"Influence of high glucose on 1,25-dihydroxyvitamin D-3-induced effect on human
                osteoblast-like MG-63 cells,"</strong> J. Bone Miner. Res. 10(7), 1050-1056, 1995.
        </p>
        <p>
            J. S. Jensen, et al., <strong>"Microalbuminuria reflects a generalized transvascular albumin leakiness in
                clinically healthy subjects,"</strong>

            Clin. Sci. 88(6), 629-633, 1995.
        </p>
        <p>
            J Am Geriatr Soc 1984 May;32(5):375-9.<strong>
                Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who
                have type II diabetes mellitus: influence of metabolic control, not age.</strong> Kabadi UM,
            Premachandra BN. "Several studies have demonstrated that the uncontrolled diabetic state in both type I as
            well as type II diabetes mellitus is characterized by altered thyroid hormone metabolism, which results in
            the<strong>
                lowering of serum triiodothyronine (T3) levels and a reciprocal elevation of T3 (rT3) levels."
            </strong>
            "Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic
            control."
        </p>
        <p>
            Metabolism 1989 Mar;38(3):278-81. <strong>The effect of fatty acids on the vulnerability of lymphocytes to
                cortisol.</strong> Klein A, Bruser B, Malkin A. "We have shown previously that cortisol-sensitive
            lymphocytes (thymocytes) have a much lower capacity than cortisol-resistant cells to catabolize cortisol and
            that <strong>linoleic acid inhibits the catabolism of cortisol by lymphocytes and modulates the sensitivity
                of lymphocytes to cortisol.</strong>" "Measuring the effect of fatty acids on cortisol catabolism by
            lymphocytes indicated that <strong>the polyunsaturated fatty acids, linoleate, arachidonate, and
                eicosapentaenoic, inhibit cortisol catabolism by lymphocytes." "Examining the effect of fatty acids on
                the vulnerability of lymphocytes to cortisol, we noted that saturated fatty acids had no significant
                effect, whereas the aforementioned polyunsaturated fatty acids make lymphocytes more sensitive to
                cortisol."</strong>
        </p>

        <p>
            Jpn J Pharmacol 1978 Apr;28(2):277-87. <strong>Relationship between cerebral energy failure and free fatty
                acid accumulation following prolonged brain ischemia.</strong>
            Kuwashima J, Nakamura K, Fujitani B, Kadokawa T, Yoshida K, Shimizu M. "Mitochondria isolated from the
            ischemic brain showed an impairment of oxidative phosphorylation. The ischemic<strong>
                brain was also characterized by remarkable accumulation of free fatty acids known to have properties as
                an uncoupling factor." "These results indicate that cerebral energy failure in the ischemic brain is
                related to the accumulation of free fatty acids, which are derived from endogenous brain
                lipids."</strong>
        </p>
        <p>
            Probl Endokrinol (Mosk) 1992 Nov-Dec; 38(6):53-4. <strong>[Effect of protein content in rat diet on
                water-soluble vitamin metabolism in streptozotocin-induced diabetes]
            </strong>[Article in Russian] Kodentsova VM, Sadykova RE, Dreval' AV, Vrzhesinskaia OA, Sokol'nikov AA,
            Beketova NA. Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced
            diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A
            high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease
            but reduced 4-pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to
            an increase of liver nicotinamide coenzymes levels and of 1-methylnicotinamide urinary excretion reflects
            increased niacin synthesis from<strong>
                the diet protein tryptophan, for niacin level is reduced in diabetes.</strong>
        </p>
        <p>
            M. Kusunoki, et al., <strong>"Amelioration of high fat feeding-induced insulin resistance in skeletal muscle
                with the antiglucocorticoid RU486,"
            </strong>

            Diabetes 44(6), 718-720, 1995. <strong>"These results suggest that glucocorticoids play, in a
                tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by
                high-fat feeding."</strong>
        </p>
        <p>
            J Neuroendocrinol 2001 Sep;13(9):827-35. <strong>A new perspective on glucocorticoid feedback: relation to
                stress, carbohydrate feeding and feeling better.
            </strong>Laugero KD. "In this review, I discuss findings that have led us to view glucocorticoid feedback in
            the HPA axis in a new light. Much of what has precipitated this view comes from a very surprising finding in
            our laboratory; sucrose ingestion normalizes feeding, energy balance and central corticotropin releasing
            factor expression in adrenalectomized (ADX) rats." "Taken together, recent findings of the well-known
            importance of glucocorticoids to feeding and energy balance, and the modulatory actions of carbohydrate
            ingestion on both basal and stress-induced activity in the HPA axis, strongly suggest that many metabolic
            (e.g. obesity) and psychological (e.g. depression) pathologies, which often present together and have been
            associated with stress and HPA dysregulation, might, in part, be understood in light of our new view of
            glucocorticoid feedback."
        </p>
        <p>
            Endocrinology 2001 Jul;142(7):2796-804. <strong>Sucrose ingestion normalizes central expression of
                corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a
                glucocorticoid-metabolic-brain axis?</strong>
            Laugero KD, Bell ME, Bhatnagar S, Soriano L, Dallman MF. "Both CRF and norepinephrine (NE) inhibit food
            intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases
            attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH
            secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are
            corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking
            sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH." <strong>"Voluntary
                ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food
                intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to
                normal."</strong>
        </p>
        <p>
            A. Lazarow, "Protection against alloxan diabetes," Anat. Rec. 97, 353, 1947.
        </p>

        <p>
            A. Lazarow, "Protective effect of glutathione and cysteine against alloxan diabetes in the rat," Proc. Soc.
            Exp. Biol. &amp; Med. 61, 441-447, 1946. <strong>[While certain doses of cysteine, glutathione, and
                thioglycolic acid completely prevented alloxan diabetes, it was interesting that all of the rats
                receiving ascorbic acid became diabetic. To me, this argues for the free radical cause of diabetes,
                rather than just the sulfhydryl oxidation. Lazarow suggested that succinic dehydrogenase, and various
                other sulfhydryl enzymes, including those involved in fatty acid oxidation, might be involved.]</strong>
        </p>
        <p>
            Minerva Endocrinol 1990 Oct-Dec;15(4):273-7. <strong>
                [Postprandial thermogenesis and obesity: effects of glucose and fructose].</strong>
            [Article in Italian] Macor C, De Palo C, Vettor R, Sicolo N, De Palo E, Federspil G. "Energy expenditure was
            calculated both in basal conditions and during the test (resting metabolic rate: RMR) using indirect
            calorimetry expressed per kg of lean weight, as assessed using bioimpedance measurement techniques. Blood
            samples were collected to assay glycemia and insulinemia. Results show that increased RMR induced by glucose
            was significantly reduced in the group of obese subjects compared to controls. <strong>In the same group of
                obese subjects, RMR was found to be significantly higher following fructose in comparison to the glucose
                response but did not differ from that in controls.</strong> Data confirm the existence of reduced
            thermogenesis in obese subjects induced by glucose. The fact that this phenomenon was not recorded in the
            same subjects following the fructose tolerance test, whose metabolism is insulin-independent, supports the
            hypothesis that reduced glucose-induced thermogenesis in obese subjects may depend on insulin resistance."
        </p>

        <p>
            Diabetes Care 2000 Oct;23(10):1472-7. <strong>Dietary unsaturated fatty acids in type 2 diabetes: higher
                levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic
                acid-rich olive oil diet.</strong> Madigan C, Ryan M, Owens D, Collins P, Tomkin GH.
        </p>
        <p>
            Proc Natl Acad Sci U S A 1990 Nov;87(22):8845-9. <strong>Incorporation of marine lipids into mitochondrial
                membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for
                enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty Acids.</strong>
            Malis CD, Weber PC, Leaf A, Bonventre JV. "Mitochondrial site 1 (NADH coenzyme Q reductase) activity was
            reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. <strong
            >Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at
                the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly
                treated mitochondria of beef-tallow-fed rats."</strong> "<strong>Phospholipase A2 activity and
                mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty
                acids."</strong>
        </p>
        <p>
            FEBS Lett 1998 Oct 16:437(1-2):24-8. <strong>Generation of protein carbonyls by glycoxidation and
                lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids.
            </strong>

            Miyata T, Inagi R, Asahi K, Yamada Y, Horie K, Sakai H, Uchida K, Kurokawa K. "In vitro incubation of
            proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and pentosidine,
            and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and
            HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and pentosidine, but
            not protein carbonyls." <strong>"The present study suggests that ascorbate and polyunsaturated fatty acids,
                but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and
                lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases."</strong>
        </p>
        <p>
            Chem Phys Lipids 1996 Jan 25;79(1):47-53. <strong>Previously unknown aldehydic lipid peroxidation compounds
                of arachidonic acid.
            </strong>
            Mlakar A, Spiteller G. Lehrstuhl fr Organische Chemie I, "Arachidonic acid was oxidized by iron ascorbate."
            "<strong>The main aldehydic lipid peroxidation product was found to be the well-known 4-hydroxy-2-nonenal
                (HNE), but 2-hydroxy heptanal (HH) -- a previously unknown lipid peroxidation product of arachidonic
                acid -- was detected to be nearly equally abundant. Malondialdehyde (MDA), glyoxal and
                2-hydroxy-4-decenal (HDE) were detected to be produced in up to 100 times lower amounts compared to
                HNE.". . . .</strong> "Since this and analogous hydroxy acids (LOHs) are the main biological
            degradation<strong>
                products of hydroperoxides of unsaturated acids (LOOHs) their further peroxidation seems to be a main
                source of toxic aldehydes."</strong>
        </p>
        <p>
            J Clin Endocrinol Metab 2000 Dec;85(12):4515-9. <strong>Acute fructose administration decreases the glycemic
                response to an oral glucose tolerance test in normal adults.</strong> Moore MC, Cherrington AD, Mann SL,
            Davis SN. "In animal models, a small (catalytic) dose of fructose administered with glucose decreases the
            glycemic response to the glucose load." "<strong>In conclusion, low dose fructose improves the glycemic
                response to an oral glucose load in normal adults without significantly enhancing the insulin or
                triglyceride response. Fructose appears most effective in those normal individuals who have the poorest
                glucose tolerance."</strong>
        </p>

        <p>
            Tumour Biol 1988;9(5):225-32. <strong>Modulation of cell-mediated immune response by steroids and free fatty
                acids in AIDS patients: a critical survey.</strong>
            Nunez EA. "The overall data presented in this review show that cortisol and free fatty acids, <strong>in
                particular long-chain polyunsaturated fatty acids, each have immunoinhibitory properties</strong> on
            lymphoblastic transformation of certain T lymphocytes. This effect is enhanced when the two factors are
            associated. These data could explain in part the immunosuppression observed in acquired immunodeficiency
            syndrome (AIDS) patients <strong>where enhanced concentrations of cortisol and polyunsaturated fatty acids
                have been observed</strong>." "These new weapons could be the administration of diets or treatments
            (liposomes) modifying the lipid profile of circulating cells and/or viruses and the utilization of hormonal
            therapy in AIDS and in some types of cancer which often present a biologic picture similar to that of AIDS."
        </p>
        <p>
            Diabetes Care 1984 Sep-Oct;7(5):465-70. <strong>Effect of protein ingestion on the glucose and insulin
                response to a standardized oral glucose load.</strong>
            Nuttall FQ, Mooradian AD, Gannon MC, Billington C, Krezowski P. "The plasma glucose area above the baseline
            following a glucose meal was reduced 34% when protein was given with the glucose." "The insulin area
            following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml,
            respectively)." "When various amounts of protein were given with 50 g glucose, the insulin area response was
            essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as
            two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but
            were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33%
            less than after the first meal. Following the second glucose + protein meal the plasma glucose area was
            markedly reduced, being only 7% as large as after the first meal. <strong>These data indicate that protein
                given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some
                type II diabetic persons."</strong> Randomized Controlled Trial
        </p>

        <p>
            Biochem J 1985 Sep 1;230(2):329-37. <strong>Inhibitory effects of some long-chain unsaturated fatty acids on
                mitochondrial beta-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial beta-oxidation
                of polyunsaturated fatty acids.</strong> Osmundsen H, Bjornstad K.<strong>
                "Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be
                powerful inhibitors of mitochondrial beta-oxidation is presented. This inhibitory property is, however,
                also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position
                of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is
                suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters
                in the mitochondrial matrix."
            </strong>
        </p>
        <p>
            Free Radic Biol Med 1999 Oct;27(7-8):901-10. <strong>Thyroid status modulates glycoxidative and lipoxidative
                modification of tissue Proteins.
            </strong>
            Pamplona R, Portero-Otin M, Ruiz C, Bellmunt MJ, Requena JR, Thorpe SR, Baynes JW, Romero M, Lopez-Torres M,
            Barja G. Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct
            formation and the half-life of the protein. <strong>Thyroid hormones are physiologic modulators of both
                tissue oxidative stress and protein degradation.</strong>
            <strong>The levels of the glycation product </strong>
            N(epsilon)-fructoselysine (FL) and those of the <strong>oxidation products, </strong>

            N(epsilon)-(carboxymethyl)lysine (CML) and<strong> malondialdehyde-lysine</strong>
            (MDA-lys), identified by GC/MS in liver proteins, <strong>decreased significantly in hyperthyroid
                rats,</strong> as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for
            advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic
            proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly
            increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as
            8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The
            results suggests that the steady state levels of these markers depend on the levels of thyroid hormones,
            presumably through their<strong>
                combined effects on the rates of protein degradation and oxidative stress,</strong> whereas DNA is more
            protected from oxidative damage.
        </p>
        <p>
            Metabolism 1999 Mar;48(3):406-9. <strong>The blood vessel, linchpin of diabetic lesions.</strong>

            Plante GE, Alfred J, Chakir M. "The morbidity and mortality associated with diabetes mellitus are
            essentially related to the vascular lesions that develop over time in this condition. Both the
            macrocirculation and microcirculation are involved, and as a consequence, vital organs such as the brain,
            retina, heart, and kidney and the limbs become damaged." "Changes in the structure of conduit arteries,
            partly responsible for the alteration in compliance characteristics, could well be related to the way these
            arteries are fed by the vasa vasorum system." "Preliminary results indicate that the size of terminal
            arterioles of the vasa vasorum (increased diameter) and the capillary permeability to albumin (markedly
            enhanced) in this specialized network are profoundly affected in the thoracic aorta obtained from diabetic
            animals. Albumin extravasation into the interstitial fluid compartment of the aorta is likely to lead to
            structural and physicochemical changes: in fact, removal of interstitial macromolecules via lymphatic
            drainage is poor in the blood vessel wall of large arteries."
        </p>
        <p>
            Metabolism 2001 Dec;50(12):1472-8. <strong>
                Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients.
            </strong>Pelikanova T, Kazdova L, Chvojkova S, Base J. <strong>"Increased contents of highly unsaturated n-6
                family FA (P &lt;.01), arachidonic acid in particular . . . were found in all groups of diabetics
                compared with HS [healthy subjects],</strong> while lower levels of linoleic acid were seen in DMN (P
            &lt;.001) and DMH (P &lt;.05). The contents of saturated FA and monounsaturated FA were comparable in HS,
            DMN, and DMD."
        </p>
        <p>
            J Clin Invest 2002 Mar;109(6):805-15. <strong>Acute intensive insulin therapy exacerbates diabetic
                blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF.</strong> Poulaki V, Qin W,
            Joussen AM, Hurlbut P, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. "Here we demonstrate that acute
            intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats."
            "Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy. . . ." "<strong
            >To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of
                diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of
                intensive insulin therapy."</strong>
        </p>

        <p>
            Acta Endocrinol (Copenh) 1992 Apr;126(4):378-80. <strong>Lipid peroxidation in early experimental diabetes
                in rats: effects of diabetes and insulin.</strong>
            Rungby J, Flyvbjerg A, Andersen HB, Nyborg K. "In the kidney, lipid<strong>
                peroxidation was increased after one week of diabetes; insulin treatment reduced the level of lipid
                peroxidation to levels lower than seen in controls. In the liver, diabetes caused an increased lipid
                peroxidation, which could be reversed by insulin; no additional effect of insulin was found. In heart
                and pancreas no effects of diabetes or insulin were demonstrated. The present paper provides</strong>
            evidence that lipid peroxidation is increased in the early stages of<strong>
                experimental diabetes and is reversible by insulin treatment. Hyperinsulinaemia may, in itself,
                counteract lipid peroxidation in kidney."</strong>
        </p>
        <p>
            Br J Nutr 1997 Sep;78(3):459-67. <strong>Influence of dietary protein and fat on serum lipids and metabolism
                of essential fatty acids in rats.</strong> Ratnayake WM, Sarwar G, Laffey P. A "In general, the
            concentrations of serum triacylglycerols and<strong>
                total cholesterol and liver phospholipid levels of arachidonic acid (AA) and docosahexaenoic acid (DHA)
                were higher in rats fed on casein diets compared with those fed on the gelatin diets. These effects were
                more pronounced in rats fed</strong> on the high-casein (300 g/kg)-high-fat (150 g/kg) diet. <strong
            >Gelatin was hypocholesterolaemic and also suppressed the liver phospholipid levels of AA and DHA (reported
                for the first time).</strong> The difference in the amino acid composition between casein and gelatin
            may be responsible for the observed effects. Casein contains higher levels of glutamic acid, methionine,
            phenylalanine and tyrosine, while gelatin contains higher levels of arginine, glycine and hydroxyproline."
        </p>

        <p>
            Br Med J 1979 Jun 30;1(6180):1753-6. <strong>Improved glucose control in maturity-onset diabetes treated
                with high-carbohydrate-modified fat diet.</strong> Simpson RW, Mann JI, Eaton J, Moore RA, Carter R,
            Hockaday TD. "Fourteen patients with established maturity-onset diabetes were treated as outpatients with a
            high-carbohydrate-(about 60% of total daily energy requirements)-modified fat diet (ratio of polyunsaturated
            fatty acids to other fatty acids greater than or equal to 1:1) for six weeks." <strong>"The findings suggest
                that it is no longer justifiable to prescribe a low-carbohydrate diet for maturity-onset
                diabetes."</strong>
        </p>
        <p>
            Postgrad Med J 1981 Aug;57(670):511-5. <strong>Severe hypertriglyceridaemia responding to insulin and
                nicotinic acid therapy.</strong> Smith SR. "Treatment with insulin and restriction of dietary
            carbohydrate led to a 50% reduction in the triglyceride concentration, and the addition of nicotinic acid in
            modest doses led ultimately to a complete normalization of the patient's lipid values. A close
            correlation<strong>
                was noted between the falling triglyceride concentration and the rising serum sodium concentration
                during the course of successful therapy. Overall, it is felt likely that this patient's severe and
                reversible hypertriglyceridaemia was on the basis of excessively rapid lipolysis
            </strong>leading to high concentrations of very low density lipoprotein production."
        </p>
        <p>
            Am J Clin Nutr 1993 Nov;58(5 Suppl):766S-770S. <strong>Fructose and dietary thermogenesis.</strong> Tappy L,
            Jequier E. "<strong>Fructose ingestion induces a greater thermogenesis than does glucose. This can be
                explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol
                glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in
                obligatory thermogenesis.</strong> Obese individuals and obese patients with non-insulin-dependent
            diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. <strong>These individuals in
                contrast display a normal thermogenesis after ingestion of fructose.</strong>

            This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin."
        </p>
        <p>
            Diabetes 2002 Jun;51(6):1772-8. <strong>
                Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances
                pancreatic islet beta-cell function.</strong>
            Tran PO, Gleason CE, Robertson RP.
        </p>
        <p>
            Proc Natl Acad Sci U S A 1998 Apr 28;95(9):4882-7. <strong>Protein-bound acrolein: potential markers for
                oxidative stress.</strong>
            <hr />
            <strong>
                Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product
                that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was
                rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative
                marker of oxidatively modified proteins under oxidative stress." "</strong>Immunohistochemical analysis
            of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6
            indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived
            foam cells and the thickening neointima of arterial walls. <strong>The observations that (i) oxidative
                modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts
                and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein</strong>

            resulted in the formation of antigenic materials suggested that<strong>
                polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein.
                These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and
                long-term damage to protein in aging, atherosclerosis, and diabetes."</strong>
        </p>
        <p>
            J Intern Med 1990 Aug;228(2):165-71. <strong>Dietary supplementation with n-3 fatty acids may impair glucose
                homeostasis in patients with non-insulin-dependent diabetes mellitus.</strong> Vessby B, Boberg M. "The
            blood glucose concentration<strong>
                tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under
                the two regimes being significantly different (P less than 0.01). In addition, the rate constant for
                glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the
                peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase</strong> during
            administration of the placebo, there being a significant difference (P less than 0.03) between the changes
            during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral
            insulin sensitivity is still unclear."
        </p>
        <p>
            Diabet Med 1992 Mar;9(2):126-33. <strong>Polyunsaturated fatty acids may impair blood glucose control in
                type 2 diabetic Patients.</strong> Vessby B, Karlstrom B, Boberg M, Lithell H, Berne C. "<strong><hr
                /></strong>
        </p>

        <p>
            Drugs 1999;58 Suppl 1:31-9; discussion 75-82. <strong>The antihyperglycaemic effect of metformin:
                therapeutic and cellular mechanisms.</strong> Wiernsperger NF, Bailey CJ "Other effects involved in the
            blood<strong>
                glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation
                and a reduction in hypertriglyceridaemia. These effects reduce the energy supply for gluconeogenesis and
                serve to balance the glucose-fatty acid (Randle) cycle."
            </strong>
        </p>
        <p>
            J Biol Chem 2001 Mar 30;276(13):9800-7. <strong>Polyunsaturated fatty acids suppress hepatic sterol
                regulatory element-binding protein-1 expression by accelerating transcript decay.
            </strong>Xu J, Teran-Garcia M, Park JH, Nakamura MT, Clarke SD. "Our initial studies<strong>
                indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear
                run-on assays suggested PUFA reduced SREBP-1 mRNA by</strong> post-transcriptional mechanisms." "<strong
            >Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay</strong> remains to be determined,
            cloning and sequencing of the 3'-untranslated region for the rat SREBP-1 transcript revealed the presence of
            an A-U-rich region that is characteristic of a destablizing element."
        </p>

        <p>
            Recent Adv Stud Cardiac Struct Metab 1976 May 26-29;12:271-7. <strong>Arrhythmogenic effects of acute free
                fatty acid mobilization on ischemic heart.</strong>
            Yamazaki N, Suzuki Y, Kamikawa T, Ogawa K, Mizutani K, Kakizawa N, Yamamoto M.
        </p>
        <p>
            Science 1978 Jul 28;201(4353):358-60. <strong>Brain edema: induction in cortical slices by polyunsaturated
                fatty acids.
            </strong>
            Chan PH, Fishman RA The presence of polyunsaturated and saturated fatty acids in leukocytic membranes
            prompted study of their possible role in the induction of brain edema. Polyunsaturated fatty acids including
            sodium arachidonate, sodium linoleate, sodium linolenate, and docasahexaenoic acids induced edma in slices
            of rat brain cortex. <strong>This cellular edema was specific, since neither saturated fatty acids nor a
                fatty acid containing a single double bond had such effect.</strong>
        </p>
        <p>
            J Neurochem 1986 Oct;47(4):1181-9. <strong>Effects of arachidonic acid on glutamate and gamma-aminobutyric
                acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons.</strong> Yu AC, Chan
            PH, Fishman RA. "Arachidonic acid inhibited glutamate uptake in both astrocytes and neurons. The inhibitory
            effect was observed within 10 min of incubation with arachidonic acid and reached approximately 80% within
            120 min in both types of culture. The arachidonic acid effect was not only time-dependent, but also
            dose-related. Arachidonic acid, at concentrations of 0.015 and 0.03 mumol/mg protein, significantly
            inhibited glutamate uptake in neurons, whereas 20 times higher concentrations were required for astrocytes.
            The effects of arachidonic acid were not as deleterious on GABA uptake as on glutamate uptake in both
            astrocytes and neurons." "<strong>Other polyunsaturated fatty acids, such as docosahexaenoic acid, affected
                amino acid uptake in a manner similar to arachidonic acid in both astrocytes and neurons. However,
                saturated fatty acids, such as palmitic acid, exerted no such effect."
            </strong>
        </p>

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