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            <strong>
                Glucose and sucrose for diabetes</strong>
        </p>Diabetes has been known since ancient times as a wasting disease in which sugar was lost in the urine, but
        more recently the name has been used to describe the presence of more than the normal amount of glucose in the
        blood, even in the absence of glucose in the urine. Some of the medical ideas regarding the original form of the
        condition have been applied to the newer form. Cultural "paradigms" or ideologies are so convenient that people
        often don't bother to doubt them, and they are sometimes so rigorously enforced that people learn to keep their
        doubts to themselves. Public concern about diabetes has been growing for decades, but despite the introduction
        of insulin and other drugs to treat it, and massive campaigns to "improve" eating habits, mortality from
        diabetes has been increasing during the last 100 years. Diabetes ("type 1") has been increasing even among
        children (Barat, et al., 2008).A basic meaning of homeopathic medicine is the support of the organism's ability
        to heal itself; the essence of allopathy is that the physician fights "a disease" to cure the patient, e.g., by
        cutting out tumors or killing germs. Confidence in the organism's essential rationality led the doctors with a
        homeopathic orientation to see a fever as part of a recuperative process, while their allopathic opponents
        sometimes saw fever as the essence of the sickness to be cured. Homeopaths concentrated on the nature of the
        patient; allopaths concentrated on a disease entity in itself, and were likely to ignore the patient's
        idiosyncrasies and preferences.Diabetes was named for the excessive urination it causes, and for the sugar in
        the urine. It was called the sugar disease, and physicians were taught that sugar was the problem. Patients were
        ordered to avoid sweet foods, and in hospitals they were sometimes locked up to keep them from finding sweets.
        The practice was derived from ideology, not from any evidence that the treatment helped.In 1857, M. Piorry in
        Paris and William Budd in Bristol, England, reasoned that if a patient was losing a pound of sugar every day in
        10 liters of urine, and was losing weight very rapidly, and had an intense craving for sugar, it would be
        reasonable to replace some of the lost sugar, simply because the quick weight loss of diabetes invariably led to
        death. Keeping patients from eating what they craved seemed both cruel and futile. After Budd's detailed reports
        of a woman's progressive recovery over a period of several weeks when he prescribed 8 ounces of sugar every day,
        along with a normal diet including beef and beef broth, a London physician, Thomas Williams, wrote sarcastically
        about Budd's metaphysical ideas, and reported his own trial of a diet that he described as similar to Budd's.
        But after two or three days he decided his patients were getting worse, and stopped the experiment. Williams'
        publication was presented as a scientific refutation of Budd's deluded homeopathic ideas, but Budd hadn't
        explained his experiment as anything more than an attempt to slow the patient's death from wasting which was
        sure to be the result of losing so much sugar in the urine. The following year Budd described another patient, a
        young man who had become too weak to work and who was losing weight at an extreme rate. Budd's prescription
        included 8 ounces of white sugar and 4 ounces of honey every day, and again, instead of increasing the amount of
        glucose in the urine, the amount decreased quickly as the patient began eating almost as much sugar as was being
        lost initially, and then as the loss of sugar in the urine decreased, the patient gained weight and recovered
        his strength. Drs. Budd and Piorry described patients recovering from an incurable disease, and that has usually
        been enough to make the medical profession antagonistic. Even when a physician has himself diagnosed diabetes
        and told a patient that it would be necessary to inject insulin for the rest of his life, if that patient
        recovers by changing his diet, the physician will typically say that the diagnosis was wrong, because diabetes
        is incurable.Twenty-five years ago, some rabbits were made diabetic with a poison that killed their
        insulin-secreting pancreatic beta-cells, and when some of them recovered from the diabetes after being given
        supplemental DHEA, it was found that their beta-cells had regenerated. The more recent interest in stem cells
        has led several research groups to acknowledge that in animals the insulin-producing cells are able to
        regenerate. It is now conceivable that there will be an effort to understand the factors that damage the
        beta-cells, and the factors that allow them to regenerate. The observations of Budd and Piorry would be a good
        place to start such a reconsideration. For many years, physicians have been taught that diabetes is either
        "genetic" or possibly caused by a viral infection, that might trigger an "autoimmune reaction," but the study of
        cellular respiration and energy metabolism and endocrinology has provided more convincing explanations. The
        antibodies that are found in the "autoimmune" conditions are evidence of tissue damage, but the damage may have
        been done by metabolic toxins, with the immune system's involvement being primarily the removal of defective
        cells. In the 1940s, Bernardo Houssay found that coconut oil protected animals from poison-induced diabetes,
        while a lard-based diet failed to protect them. Later, glucose itself was found to protect the pancreatic
        beta-cells from poisons.In 1963, P.J. Randle clearly described the inhibition of glucose oxidation by free fatty
        acids. Later, when lipid emulsions came into use for intravenous feeding in hospitals, it was found that they
        blocked glucose oxidation, lowered the metabolic rate, suppressed immunity, and increased lipid peroxidation and
        oxidative stress.Estrogen and stress are both known to create some of the conditions of diabetes, while
        increasing fat oxidation and inhibiting glucose oxidation. Emotional stress, overwork, trauma, and infections
        have been known to initiate diabetes. Estrogen increases free fatty acids and decreases glycogen storage, and
        when birth control pills were becoming popular, some researchers warned that they might cause diabetes. But the
        food oil industry and the estrogen industry were satisfied with the medical doctrine that diabetes was caused by
        eating too much sugar.If the essence of diabetes is the presence of too much sugar, then it seems reasonable to
        argue that it is the excess sugar that's responsible for the suffering and death associated with the disease,
        otherwise, how would the prohibition of sugar in the diet be justified? In fact, the argument is made (e.g.,
        Muggeo, 1998) that it is the hyperglycemia that causes problems such as hypertension, kidney failure, heart
        failure, neuropathy, blindness, dementia, and gangrene.As information about the many physiological and
        biochemical events associated with diabetes has accumulated, the basic doctrine that "sugar causes diabetes" has
        extended itself to whatever the topic of discussion is<strong>: </strong>"Glucose causes" the death of
        beta-cells, glucose causes blood vessels to become leaky, glucose causes cells to be unable to absorb glucose,
        glucose causes the formation of free radicals, glucose impairs immunity and wound healing, but causes
        inflammation while preventing the "respiratory burst" in which free radicals are produced by cells that cause
        inflammation, it disturbs enzyme functions, impairs nerve conduction and muscle strength, etc., and it is also
        addictive, causing people to irrationally seek the very material that is poisoning them. Tens of thousands of
        publications describe the pathogenic effects of sugar. To prove their point, they grow cells in a culture dish,
        and find that when they are exposed to excess glucose, often 5 times the normal amount, they deteriorate. In the
        artificial conditions of cell culture, the oversupply of glucose causes lactic acid to accumulate, leading to
        toxic effects. But in the organism, the hyperglycemia is compensating for a sensed deficiency of glucose, a need
        for more energy. If diabetes means that cells can't absorb or metabolize glucose, then any cellular function
        that requires glucose will be impaired, despite the presence of glucose in the blood. It is the intracellular
        absence of glucose which is problematic, rather than its extracellular excess. Neuroglycopenia (or
        neuroglucopenia) or intracellular glycopenia refers to the deficit of glucose in cells. When the brain senses a
        lack of glucose, nerves are activated to increase the amount of glucose in the blood, to correct the problem. As
        long as the brain senses the need for more glucose, the regulatory systems will make the adjustments to the
        blood glucose level. The antagonism between fat and sugar that Randle described can involve the suppression of
        sugar oxidation when the concentration of fats in the bloodstream is increased by eating fatty food, or by
        releasing fats from the tissues by lipolysis, but it can also involve the suppression of fat oxidation by
        inhibiting the release of fatty acids from the tissues, when a sufficient amount of sugar is eaten. When a
        normal person, or even a "type 2 diabetic," is given a large dose of sugar, there is a suppression of lipolysis,
        and the concentration of free fatty acids in the bloodstream decreases, though the suppression is weaker in the
        diabetic (Soriguer, et al., 2008). Insulin, released by the sugar, inhibits lipolysis, reducing the supply of
        fats to the respiring cells.Free fatty acids suppress mitochondrial respiration (Kamikawa and Yamazaki, 1981),
        leading to increased glycolysis (producing lactic acid) to maintain cellular energy. The suppression of
        mitochondrial respiration increases the production of toxic free radicals, and the decreased carbon dioxide
        makes the proteins more susceptible to attack by free radicals. The lactate produced under the influence of
        excessive fat metabolism stimulates the release of endorphins, which are lipolytic, releasing more free fatty
        acids from the tissues. Acting through cytokines such as interleukin-6, lactate shifts the balance toward the
        catabolic hormones, leading to tissue wasting.Lactic acid itself, and the longer chain fatty acids, inhibit the
        regulatory enzyme pyruvate dehydrogenase (which is activated by insulin), reducing the oxidative production of
        energy. Drugs to activate this enzyme are being studied by the pharmaceutical industry as treatments for
        diabetes and cancer (for example, DCA, dichloroacetate).Oxidative damage of proteins is often described as
        glycation or glycosylation, but it really consists of many addition and crosslinking reactions, most often onto,
        or between, lysine groups. Carbon dioxide normally associates with lysine groups, so the destructive reactions
        are favored when carbon dioxide is displaced by lactic acid. The reactive fragments of polyunsaturated fatty
        acids are much more often the source of the protein-damaging radicals than the carbohydrates are. The importance
        of the fats in causing type-2 diabetes is coming to be accepted, for example Li, et al., recently (2008) said
        "The cellular link between fatty acids and ROS (reactive oxygen species) is essentially the mitochondrion, a key
        organelle for the control of insulin secretion. Mitochondria are the main source of ROS and are also the primary
        target of oxidative attacks."But much earlier (Wright, et al., 1988) it had been demonstrated that a deficiency
        of the "essential fatty acids" prevents toxin-induced diabetes and greatly increases resistance to inflammation
        (Lefkowith, et al., 1990). The lack of those so-called "essential fatty acids" also prevents autoimmune diabetes
        in a strain of diabetic mice (Benhamou, et al., 1995),Suppressing fatty acid oxidation improves the contraction
        of the heart muscle and increases the efficiency of oxygen use (Chandler, et al., 2003). Various drugs are being
        considered for that purpose, but niacinamide is already being used to improve heart function, since it lowers
        the concentration of free fatty acids.The antimetabolic and toxic effects of the polyunsaturated fatty acids can
        account for the "insulin resistance" that characterizes type-2 diabetes, but similar actions in the pancreatic
        beta-cells can impair or kill those cells, creating a deficiency of insulin, resembling type-1 diabetes.The
        suppression of mitochondrial respiration causes increased free radical damage, and the presence of
        polyunsaturated fatty acids in the suppressed cell increases the rate of fat decomposition and production of
        toxins.Increasing the rate of respiration by replacing the fats with glucose reduces the availability of
        electrons that can trigger lipid peroxidation and produce toxic free radicals, and the shift of fuel also
        increases the amount of carbon dioxide produced, which can protect the protein amino groups such as lysine from
        glycation and lipoxidation.While it's clear that it is the excessive oxidation of fat that damages cells in the
        "diabetic" state in which cells aren't able to use glucose, it's important to look at some of the situations in
        which so many researchers are blaming problems on hyperglycemia.Important problems in diabetes are slow wound
        healing, excessive permeability or leakiness of blood vessels which allows molecules such as albumin to be
        extravasated, and the impaired function and survival of pancreatic beta-cells.During the healing of a wound in a
        diabetic individual, the local concentration of glucose decreases and then entirely disappears, as healing
        stops. Applying glucose and insulin topically to the wound, it heals quickly. The very old practice of treating
        deep wounds with honey or granulated sugar has been studied in controlled situations, including the treatment of
        diabetic ulcers, infected deep wounds following heart surgery, and wounds of lepers. The treatment eradicates
        bacterial infections better than some antiseptics, and accelerates healing without scarring, or with minimal
        scarring. The sugar regulates the communication between cells, and optimizes the synthesis of collagen and
        extracellular matrix. An excess of insulin, causing hypoglycemia, can cause blood vessels, for example in the
        brain and kidneys, to become leaky, and this has been claimed to be an effect of insulin itself. However, the
        same leakiness can be produced by an analog of glucose that can't be metabolized, so that intracellular
        glycopenia is produced. The harmful effect that has been ascribed to excessive insulin can be prevented by
        maintaining an adequate supply of glucose (Uezu and Murakami, 1993), showing that it is the lack of glucose,
        rather than the excess insulin, that causes the vascular malfunction. Fructose also reduces the leakiness of
        blood vessels (Plante, et al., 2003). Many of the complications of diabetes are caused by increased vascular
        leakiness (Simard, et al., 2002).Sugar can protect the beta-cells from the free fatty acids, apparently in the
        same ways that it protects the cells of blood vessels, restoring metabolic energy and preventing damage to the
        mitochondria. Glucose suppresses superoxide formation in beta-cells (Martens, et al., 2005) and apparently in
        other cells including brain cells.<u> </u>(Isaev, et al., 2008).The beta-cell protecting effect of glucose is
        supported by bicarbonate and sodium. Sodium activates cells to produce carbon dioxide, allowing them to regulate
        calcium, preventing overstimulation and death. For a given amount of energy released, the oxidation of glucose
        produces more carbon dioxide and uses less oxygen than the oxidation of fatty acids. The toxic excess of
        intracellular calcium that damages the insulin-secreting cells in the relative absence of carbon dioxide is
        analogous to the increased excitation of nerves and muscles that can be produced by hyperventilation.In every
        type of tissue, it is the failure to oxidize glucose that produces oxidative stress and cellular damage. Even
        feeding enough sucrose to cause fat deposition in the liver can protect the liver from oxidative stress
        (Spolarics and Meyenhofer, 2000), possibly by mechanisms such as those involved in the treatment of alcoholic
        liver disease with saturated fats.The active thyroid hormone, T3, protects the heart by supporting the oxidation
        of glucose (Liu, et al., 1998). The amount of T3 produced by the liver depends mainly on the amount of glucose
        available.Animals that have been made diabetic with relatively low doses of the poison streptozotocin can
        recover functional beta-cells spontaneously, and the rate of recovery is higher in pregnant animals (Hartman, et
        al., 1989). Pregnancy stabilizes blood sugar at a higher level, and progesterone favors the oxidation of glucose
        rather than fats.A recent study suggests that recovery of the pancreas can be very fast. A little glucose was
        infused for 4 days into rats, keeping the blood glucose level normal, and the mass of beta-cells was found to
        have increased 2.5 times. Cell division wasn't increased, so apparently the additional glucose was preventing
        the death of beta-cells, or stimulating the conversion of another type of cell to become insulin-secreting
        beta-cells (Jetton, et al., 2008).That study is very important in relation to stem cells in general, because it
        either means that glandular cells are turning over ("streaming") at a much higher rate than currently recognized
        in biology and medicine, or it means that (when blood sugar is adequate) stimulated cells are able to recruit
        neighboring cells to participate in their specialized function. Either way, it shows the great importance of
        environmental factors in regulating our anatomy and physiology."Diabetologists" don't regularly measure their
        patients' insulin, but they usually make the assumption that insulin is the main factor regulating blood sugar.
        In one study, it was found that the insulin molecule itself, immunoreactive insulin, accounted for only about 8%
        of the serum's insulin-like action. The authors of that study believed that potassium was the main other factor
        in the serum that promoted the disposition of glucose. Since potassium and glucose are both always present in
        the blood, their effects on each other have usually been ignored. Cellular activation (by electrical, nervous,
        chemical, or mechanical stimulation) causes glucose to be absorbed and oxidized, even in the absence of insulin
        and in otherwise insulin-resistant individuals. I think this local interaction between the need for energy and
        the production of energy predominates in good health, with insulin and other hormones facilitating the process
        in times of stress. A variety of local tissue regulators, including GABA and glutamate, probably participate in
        these interactions, in the brain, endocrine glands, muscles, and other tissues, and are probably involved in the
        relaxing and analgesic actions of the sugars. The GABA system (GABA is highly concentrated in the beta-cells) is
        involved in regulating blood sugar, inhibiting the release of glucagon when glucose isn't needed, and apparently
        allowing the beta cells to discriminate between amino acids and glucose (Gu, et al., 1993) and acting as a
        survival and growth factor for neighboring cells (Ligon, et al., 2007). The damaged beta-cells lose the enzyme
        (glutamate dehydrogenase) that makes GABA, and their ratio of linoleic acid to saturated and monounsaturated fat
        increases, a change that corresponds to a decreased metabolism of glucose.The free intracellular calcium that
        can become toxic is normally bound safely by well-energized mitochondria, and in the bloodstream it is kept
        safely complexed with carbon dioxide. The thyroid hormone, producing carbon dioxide, helps to sustain the level
        of ionized calcium (Lindblom, et al., 2001). In a vitamin D deficiency, or a calcium deficiency, the parathyroid
        hormone increases, and this hormone can contribute to many inflammatory and degenerative processes, including
        diabetes. Consuming enough calcium and vitamin D to keep the parathyroid hormone suppressed is important to
        protect against the degenerative conditions.When animals were fed an otherwise balanced diet lacking vitamin D,
        with the addition of either 68% sucrose or 68% starch, the bones of those on the starch diet failed to develop
        normally, as would be expected with a vitamin D deficiency, and their serum calcium was low. However, the bones
        of those on the diet with sucrose developed properly, and didn't show evidence of being calcium deficient,
        though they weren't quite as heavy as those that also received an adequate amount of vitamin D (Artus, 1975).
        This study suggests that the famous dietetic emphasis on the "complex carbohydrates," i.e., starches, has made
        an important contribution to the prevalence of osteoporosis, as well as obesity and other degeneration
        conditions.Both vitamin D and vitamin K, another important calcium-regulating nutrient, are now known to prevent
        diabetes. Both of these vitamins require carbon dioxide for disposing of calcium properly, preventing its
        toxicity. When carbon dioxide is inadequate, for example from simple hyperventilation or from hypothyroidism,
        calcium is allowed to enter cells, causing inappropriate excitation, sometimes followed by calcification.Keeping
        an optimal level of carbon dioxide (for example, when adapted to high altitude) causes calcium to be controlled,
        resulting in lowered parathyroid hormone, an effect similar to supplementing with calcium, vitamin D, and
        vitamin K. (E.g., Nicolaidou, et al, 2006.) Glycine, like carbon dioxide, protects proteins against oxidative
        damage (Lezcano, et al., 2006), so including gelatin (very rich in glycine) in the diet is probably protective.
        The contribution of PTH to inflammation and degeneration is just being acknowledged (e.g., Kuwabara, 2008), but
        the mechanism undoubtedly involves the fact that it is lipolytic, increasing the concentration of free fatty
        acids that suppress metabolism and interfere with the use of glucose.When we talk about increasing the metabolic
        rate, and the benefits it produces, we are comparing the rate of metabolism in the presence of thyroid, sugar,
        salt, and adequate protein to the "normal" diet, containing smaller amounts of those "stimulating" substances.
        It would be more accurate if we would speak of the suppressive nature of the habitual diet, in relation to the
        more optimal diet, which provides more energy for work and adaptation, while minimizing the toxic effects of
        free radicals.Feeding animals a normal diet with the addition of Coca-Cola, or with a similar amount of sucrose,
        has been found to let them increase their calorie intake by 50% without increasing their weight gain
        (Bukowiecki, et al., 1983). Although plain sucrose can alleviate the metabolic suppression of an average diet,
        the effect of sugars in the diet is much more likely to be healthful in the long run when they are associated
        with an abundance of minerals, as in milk and fruit, which provide potassium and calcium and other protective
        nutrients. Avoiding the starches such as cereals and beans, and using fruits as a major part of the diet helps
        to minimize the effects of the polyunsaturated fats. Celiac disease or gluten sensitivity is associated with
        diabetes and hypothyroidism. There is a cross reaction between the gluten protein molecule and an enzyme which
        is expressed under the influence of estrogen. This is another reason for simply avoiding cereal
        products.Brewers' yeast has been used traditionally to correct diabetes, and its high content of niacin and
        other B vitamins and potassium might account for its beneficial effects. However, eating a large quantity of it
        is likely to cause gas, so some people prefer to extract the soluble nutrients with hot water. Yeast contains a
        considerable amount of estrogen, and the water extract probably leaves much of that in the insoluble starchy
        residue. Liver is another rich source of the B vitamins as well as the oily vitamins, but it can suppress
        thyroid function, so usually one meal a week is enough.The supplements that most often help to correct
        diabetes-like conditions are niacinamide, thiamine, thyroid, and progesterone or pregnenolone. Vitamins D and K
        are clearly protective against developing diabetes, and their effects on many regulatory processes suggest that
        they would also help to correct existing hyperglycemia.Drinking coffee seems to be very protective against
        developing diabetes. Its niacin and magnesium are clearly important, but it is also a rich source of
        antioxidants, and it helps to maintain normal thyroid and progesterone production. Chocolate is probably
        protective too, and it is a good source of magnesium and antioxidants.A recent study (Xia, et al., 2008) showed
        that inhibition of cholesterol synthesis by beta-cells impairs insulin synthesis, and that replenishing
        cholesterol restores the insulin secretion. Green tea contains this type of inhibitor, but its use has
        nevertheless been associated with a reduced risk of diabetes. Caffeine is likely to be the main protective
        substance in these foods. Although antioxidants can be protective against diabetes, not all things sold as
        "antioxidants" are safe; many botannical "antioxidants" are estrogenic. Hundreds of herbal products can lower
        blood sugar, but many of them are simply toxic, and the reduction of blood glucose can make some problems
        worse.The supplements I mention above--including caffeine--have antiinflammatory, antioxidative and
        energy-promoting effects. Inflammation, interfering with cellular energy production, is probably the essential
        feature of the things called diabetes.Aspirin has a very broad spectrum of antiinflammatory actions, and is
        increasingly being recommended for preventing complications of diabetes. One of the consequences of inflammation
        is hyperglycemia, and aspirin helps to correct that (Yuan, et al., 2001), while protecting proteins against
        oxidative damage (Jafarnejad, et al, 2001).If Dr. Budd's thinking (and results) had been more widely accepted
        when his publications appeared, thinking about "diabetes" might have led to earlier investigation of the
        syndromes of stress and tissue wasting, with insulin being identified as just one of many regulatory substances,
        and a large amount of useless and harmful activity treating hyperglycemia as the enemy, rather than part of an
        adaptive reaction, might have been avoided. <span style="white-space: pre-wrap"> </span>
        <h3>REFERENCES</h3>Ann Nutr Aliment. 1975;29(4):305-12. <strong>[Effects of administering diets with starch or
            sucrose basis on certain parameters of calcium metabolism in the young, growing rat]</strong> Artus
        M.Diabetes Metab. 2008 Oct 24. <strong>The growing incidence of type 1 diabetes in children: The 17-year French
            experience in Aquitaine.</strong> Barat P, Valade A, Brosselin P, Alberti C, Maurice-Tison S, L"vy-Marchal
        C.Pancreas. 1995 Jul;11(1):26-37. <strong>Essential fatty acid deficiency prevents autoimmune diabetes in
            nonobese diabetic mice through a positive impact on antigen-presenting cells and Th2 lymphocytes.</strong>
        Benhamou PY, Mullen Y, Clare-Salzler M, Sangkharat A, Benhamou C, Shevlin L, Go VL.The Retrospect of Medicine,
        XXXVII January-June, 1858 Edited by W. Braithwaite, p. 122: SUGAR AND DIABETES: A CASE. By Dr. William Budd,
        Senior Physician to the Bristol Royal Infirmary.Am J Physiol. 1983 Apr;244(4):R500-7. <strong>Effects of
            sucrose, caffeine, and cola beverages on obesity, cold resistance, and adipose tissue cellularity.</strong>
        Bukowiecki LJ, Lupien J, Foll"a N, Jahjah L.Cardiovasc Res. 2003 Jul 1;59(1):143-51. <strong>Partial inhibition
            of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia.
        </strong>Chandler MP, Chavez PN, McElfresh TA, Huang H, Harmon CS, Stanley WC.Med Sci (Paris). 2003
        Aug-Sep;19(8-9):827-33.<strong>
            [Contribution of free fatty acids to impairment of insulin secretion and action: mechanism of beta-cell
            lipotoxicity]</strong> [Article in French] Girard J.Diabetes Metab. 21(2), 79-88, 1995. <strong>Role of free
            fatty acids in insulin resistance of subjects with non-insulin-dependent diabetes,</strong> Girard J.
        "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." [This direct effect of
        free fatty acids on the beta cells is extremely important. Estrogen--probably via GH--increases free fatty
        acids, and adrenalin--which is elevated in hypothyroidism--increases the release of free fatty acids from
        storage. Free fatty acids impair mitochondrail energy production.]Med Sci (Paris). 2005 Dec;21 Spec No:19-25.
        <strong>[Contribution of free fatty acids to impairment of insulin secretion and action. mechanism of beta-cell
            lipotoxicity]</strong> Girard J.Acta Diabetologica 32(1), 44-48, 1995.<strong>Effect of lipid oxidation on
            the regulation of glucose utilization in obese patients</strong>, Golay A., et al., [Free fatty acids
        strongly and quickly depress the ability to oxidize or store glucose.]Life Sci. 1993;52(8):687-94. <strong
        >Suppressive effect of GABA on insulin secretion from the pancreatic beta-cells in the rat.</strong> Gu XH,
        Kurose T, Kato S, Masuda K, Tsuda K, Ishida H, Seino Y.Exp Clin Endocrinol 1989 May;93(2-3):225-30. <strong
        >Spontaneous recovery of streptozotocin diabetes in mice.</strong> Hartmann K, Besch W, Zuhlke H.Proc. Nat.
        Acad. Sci. USA 92(8), 3096-3099, 1995. <strong>High fat diet-induced hyperglycemia: Prevention by low level
            expression of a glucose transporter (GLUT4) minigene in transgenic mice</strong>. Ikemoto S, et al. "...mice
        fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity."
        Biochemistry (Mosc). 2008 Feb;73(2):149-55.<strong>
            Mitochondrial free radical production induced by glucose deprivation in cerebellar granule neurons.</strong>
        Isaev NK, Stelmashook EV, Dirnagl U, Plotnikov EY, Kuvshinova EA, Zorov DB.J Pharmacol Exp Ther. 2008
        Feb;324(2):850-7. <strong>Investigation of the mechanisms involved in the high-dose and long-term acetyl
            salicylic acid therapy of type I diabetic rats.</strong> Jafarnejad A, Bathaie SZ, Nakhjavani M, Hassan
        MZ.Am J Physiol Endocrinol Metab. 2008 Apr;294(4):E679-87. <strong>Enhanced beta-cell mass without increased
            proliferation following chronic mild glucose infusion.</strong> Jetton TL, Everill B, Lausier J, Roskens V,
        Habibovic A, LaRock K, Gokin A, Peshavaria M, Leahy JL.World J Surg. 2001 Feb;25(2):142-6. <strong>Effect of
            sucrose on collagen metabolism in keloid, hypertrophic scar, and granulation tissue fibroblast
            cultures.</strong> K"ssi J, V"h"-Kreula M, Peltonen J, Risteli J, Laato M.Clin Endocrinol (Oxf). 1994
        Jan;40(1):47-53. <strong>Impaired glucose tolerance and insulin insensitivity in primary
            hyperparathyroidism.</strong> Kumar S, Olukoga AO, Gordon C, Mawer EB, France M, Hosker JP, Davies M,
        Boulton AJ.Diabetes 44(6), 718-720, 1995. <strong>Amelioration of high fat feeding-induced insulin resistance in
            skeletal muscle with the antiglucocorticoid RU486.</strong> Kusunoki M, et al. "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."Osteoporos Int. 2008 Sep 30. <strong>High prevalence of vitamin K and D
            deficiency and decreased BMD in inflammatory bowel disease.</strong> Kuwabara A, Tanaka K, Tsugawa N, Nakase
        H, Tsuji H, Shide K, Kamao M, Chiba T, Inagaki N, Okano T, Kido S.Am J Physiol Cell Physiol. 2008
        Jun;294(6):C1542-51. <strong>Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the
            estrogen receptor and extracellular signal-regulated kinase pathways.
        </strong>Lee MJ, Lin H, Liu CW, Wu MH, Liao WJ, Chang HH, Ku HC, Chien YS, Ding WH, Kao YH.J Immunol 1990 Sep
        1;145(5):1523-9, <strong>Manipulation of the acute inflammatory response by dietary polyunsaturated fatty acid
            modulation,</strong>Lefkowith JB, Morrison A, Lee V, Rogers M.Rev Alerg Mex. 2006 Nov-Dec;53(6):212-6.
        <strong>Effect of glycine on the immune response of the experimentally diabetic rats.</strong> Lezcano Meza D,
        Ter"n Ortiz L, Carvajal Sandoval G, Guti"rrez de la Cadena M, Ter"n Escand"n D, Estrada Parra S.Circ Shock 1990
        Jun;31(2):159-170, <strong>Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in
            vascular permeability,</strong> Li EJ, Cook JA, Spicer KM, Wise WC, Rokach J, Halushka PV.Diabetologia. 2007
        Apr;50(4):764-73.<strong>
            Regulation of pancreatic islet cell survival and replication by gamma-aminobutyric acid.
        </strong>Ligon B, Yang J, Morin SB, Ruberti MF, Steer ML.Horm Res. 2001;55(2):81-7. <strong>Decreased levels of
            ionized calcium one year after hemithyroidectomy: importance of reduced thyroid hormones.</strong> Lindblom
        P, Valdemarsson S, Linderg"rd B, Westerdahl J, Bergenfelz A.Am J Physiol. 1998 Sep;275(3 Pt 1):E392-9. <strong
        >Acute effects of triiodothyronine on glucose and fatty acid metabolism during reperfusion of ischemic rat
            hearts.</strong> Liu Q, Clanachan AS, Lopaschuk GD.J Biol Chem. 2005 May 27;280(21):20389-96. <strong
        >Glucose suppresses superoxide generation in metabolically responsive pancreatic beta cells.</strong>Martens GA,
        Cai Y, Hinke S, Stang" G, Van de Casteele M, Pipeleers D.Diabet Med. 1998;15 Suppl 4:S60-2. <strong>Accelerated
            complications in Type 2 diabetes mellitus: the need for greater awareness and earlier detection.</strong>
        Muggeo M. "Persistent hyperglycaemia is the underlying pathogenic factor responsible for chronic diabetic
        complications in Type 1 and Type 2 diabetes mellitus."Eur J Pediatr. 2006 Aug;165(8):540-5. <strong>The effect
            of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with
            cystic fibrosis.</strong> Nicolaidou P, Stavrinadis I, Loukou I, Papadopoulou A, Georgouli H, Douros K,
        Priftis KN, Gourgiotis D, Matsinos YG, Doudounakis S.Metabolism. 2007 May;56(5):599-607. <strong>Long-term
            consumption of caffeine improves glucose homeostasis by enhancing insulinotropic action through islet
            insulin/insulin-like growth factor 1 signaling in diabetic rats.</strong> Park S, Jang JS, Hong
        SM.Cardiovasc Res. 2003 Oct 1;59(4):963-70.<strong>
            Reduction of endothelial NOS and bradykinin-induced extravasation of macromolecules in skeletal muscle of
            the fructose-fed rat model.</strong> Plante GE, Perreault M, Lanthier A, Marette A, Maheux P.Cell Physiol
        Biochem. 2007;20(1-4):213-26.<strong>
            Effect of lipid infusion on metabolism and force of rat skeletal muscles during intense
            contractions.</strong> Silveira L, Hirabara SM, Alberici LC, Lambertucci RH, Peres CM, Takahashi HK, Pettri
        A, Alba-Loureiro T, Luchessi AD, Cury-Boaventura MF, Vercesi AE, Curi R.Can J Physiol Pharmacol. 2002
        Dec;80(12):1203-7. <strong>Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced
            vascular permeability in type 1 diabetic mice.</strong> Simard B, Gabra BH, Sirois P.Obesity (Silver
        Spring). 2008 Oct 23. <strong>Changes in the Serum Composition of Free-fatty Acids During an Intravenous Glucose
            Tolerance Test.
        </strong>Soriguer F, Garc"a-Serrano S, Garc"a-Almeida JM, Garrido-S"nchez L, Garc"a-Arn"s J, Tinahones FJ,
        Cardona I, Rivas-Mar"n J, Gallego-Perales JL, Garc"a-Fuentes E.Biochim Biophys Acta. 2000 Sep
        27;1487(2-3):190-200. <strong>Augmented resistance to oxidative stress in fatty rat livers induced by a
            short-term sucrose-rich diet.</strong>Spolarics Z, Meyenhofer M.Gen Pharmacol. 1993 Jan;24(1):95-100.<strong
        >
            A possible mechanism for increased cerebrovascular permeability in diabetic rats: effects of insulin and
            2-deoxy-glucose.</strong> Uezu Y, Murakami K.Wound Repair Regen. 2008 Mar-Apr;16(2):288-93.<strong>
            Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia.</strong>
        Velander P, Theopold C, Hirsch T, Bleiziffer O, Zuhaili B, Fossum M, Hoeller D, Gheerardyn R, Chen M, Visovatti
        S, Svensson H, Yao F, Eriksson E.Proc Natl Acad Sci U S A. 1988 Aug;85(16):6137-41. <strong>Essential fatty acid
            deficiency prevents multiple low-dose streptozotocin-induced diabetes in CD-1 mice.</strong>Wright JR Jr,
        Lefkowith JB, Schreiner G, Lacy PE.Endocrinology. 2008 Oct;149(10):5136-45. <strong>Inhibition of cholesterol
            biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic beta-cells.
        </strong>Xia F, Xie L, Mihic A, Gao X, Chen Y, Gaisano HY, Tsushima RG.Science. 2001 Aug
        31;293(5535):1673-7.<strong>
            Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta.
        </strong>Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE.
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