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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of vitamin E in the pathogenesis of diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin E on some of the metabolic parameters of experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight at 12 weeks of age). Vitamin E (0.2, 0.4, 0.8 mg/kg body weight) was administered orally for a period of 3 weeks to normal and diabetic Wistar rats. In some experiments, Vitamin E was given either before or after the induction of diabetes mellitus. Blood glucose level and weight were recorded for each rat in different groups on a weekly basis. Oral glucose tolerance test (OGTT) was performed on fasted normal, diabetic and vitamin E treated rats at the end of the experiment. Vitamin E significantly (p < 0.01) reduced blood glucose levels in experimental diabetes mellitus at all doses as compared to untreated rats. Vitamin E induced weight loss in normal as well as in diabetic rats. The beneficial effect of vitamin E on the hyperglycaemia of diabetic rats was dose-dependent. Moreover, vitamin E also improved OGTT in diabetic rats compared to untreated diabetics. In conclusion, vitamin E may play a role in glucose metabolism and thus be a useful adjuvant therapy in type I diabetes.
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PMID:Beneficial effect of vitamin E on the metabolic parameters of diabetic rats. 1536 83

Mouse studies indicated that plasma phospholipid transfer protein (PLTP) determines the plasma distribution of vitamin E, a potent lipophilic antioxidant. Vitamin E distribution, antioxidant status, and titer of anti-oxidized LDLs (oxLDL) autoantibodies were evaluated in plasma from control subjects (n = 31) and type 2 diabetic patients (n = 31) with elevated plasma PLTP concentration. Unlike diabetic and control HDLs, which displayed similar vitamin E contents, diabetic VLDLs and diabetic LDLs contained fewer vitamin E molecules than normal counterparts. Plasma PLTP concentration in diabetic plasmas correlated negatively with vitamin E in VLDL+LDL, but positively with vitamin E in HDL, with an even stronger correlation with the VLDL+LDL-to-HDL vitamin E ratio. Circulating levels of oxLDL were significantly higher in diabetic plasmas than in control plasmas. Whereas the titer of IgG autoantibodies to modified LDL did not differ significantly between diabetic patients and control subjects, diabetic plasmas showed significantly lower levels of potentially protective IgM autoantibodies. The present observations support a pathophysiological role of PLTP in decreasing the vitamin E content of apolipoprotein B-containing lipoproteins, but not of HDL in plasma of type 2 diabetic patients, contributing to a greater potential for LDL oxidation.
Diabetes 2004 Oct
PMID:Alterations in plasma vitamin E distribution in type 2 diabetic patients with elevated plasma phospholipid transfer protein activity. 1544 94

In this study, solitary and combined effects of vitamin E and the calcium-channel blocker diltiazem were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male Wistar albino rats, weighing approximately 200 g were used. Diabetes mellitus was induced by a single intravenous injection of STZ at a dose of 65 mg/kg body weight. Five experimental groups were established as STZ-diabetic, STZ-diabetic + vitamin E, STZ-diabetic + diltiazem and STZ-diabetic + vitamin E + diltiazem. Vitamin E was injected intraperitoneally three times a week at a dose of 500 mg/kg body weight. Diltiazem was given orally every day at a dose of 25 mg/kg body weight. At the end of the study (10 weeks) blood glucose levels of diabetic rats, which had received vitamin E and diltiazem, had significantly decreased when compared with untreated diabetic rats (P < 0.02). Similarly, HbA1c levels had significantly decreased in diabetic rats which had received vitamin E (P < 0.05), diltiazem (P < 0.01) and vitamin E + diltiazem (P < 0.02) when compared with untreated diabetic rats. Liver glutathione levels of diabetic rats, which had received vitamin E (P < 0.01) and vitamin E + diltiazem (P < 0.05) had significantly increased when compared with untreated diabetic rats. Liver lipid peroxide levels had significantly decreased in diabetic rats, which had received vitamin E (P < 0.001) and diltiazem (P < 0.01). With respect to their metabolic and antioxidant effects, vitamin E proved superior to diltiazem.
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PMID:Comparison of the metabolic and antioxidant effects of diltiazem and vitamin E on streptozotocin-diabetic rats. 1548 59

Protein kinase C (PKC) is a family of serine/threonine kinases that regulates a variety of cell functions including proliferation, gene expression, cell cycle, differentiation, cytoskeletal organization, cell migration, and apoptosis. The PKC signal transduction cascade coordinates complex physiological events including normal tissue function and repair. Disruption of the cellular environment through genetic mutation, disease, injury, or exposure to pro-oxidants, alcohol, or other insults can induce pathological PKC activation. Aberrant PKC activation can lead to diseases of cellular dysregulation such as cancer and diabetes. Can aberrant activation of PKC be reversed? Even 25 years after the identification of PKC, therapeutic regulation of PKC activity remains an emerging field. Because the function of each isoform remains to be elucidated, isoform specific control of gene expression is a current challenge. Natural compounds are important regulators of PKC activity, with both preventive and therapeutic efficacy. Antioxidants including vitamin A (retinoids), vitamin C (ascorbic acid) and vitamin E (tocopherols) show promise for reversal of PKC activation. beta-carotene and retinoids function as anticarcinogenic agents and antagonize the biological effects of pro-oxidants on PKC. Vitamin E reverses the deleterious effects of hyperglycemia and diabetes by down-regulating PKC activity. Antioxidants in red wine provide cardioprotective effects. However, alcohol consumption also induces oxidative stress and disrupts PKC and retinoid function in the fetus and the adult. This review examines modulation of PKC activity by natural compounds and pharmacologic analogues which can be used effectively to prevent or treat common diseases associated with aberrant activation of PKC.
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PMID:Therapeutic potential of natural compounds that regulate the activity of protein kinase C. 1554 81

Hyperglycemia causes protein glycosylation, oxidation and alterations in enzyme activities, which are the underlying causes of diabetic complications. This study was undertaken to test the role of vitamin E treatment on Ca2+-ATPase activity, protein glycosylation and lipid peroxidation in the brain of streptozotocin (STZ)-induced diabetic rats. Male rats weighing about 250-300 g were rendered diabetic by a single STZ injection of 50 mg/kg via the tail vein. Both the diabetic and non-diabetic rats were fed a vitamin E supplemented diet (500 IU/kg/day). Ca2+-ATPase activity was significantly reduced at week 10 of diabetes compared to the control group (p < 0.05), with 0.225+/-0.021 U/I (mean +/- S.E.M.) in the control group and 0.072 +/- 0.008 U/l (mean +/- S.E.M.) in the diabetic group. Vitamin E treatment prevented the enzyme activity from decreasing. The activities observed were 0.226 +/- 0.020 U/l and 0.172 +/- 0.011 U/I (mean +/- S.E.M.) in the vitamin E-treated control and diabetic group, respectively. STZ-induced diabetes resulted in an increased protein glycosylation and lipid peroxidation. Vitamin E treatment led to a significant inhibition in blood glucose, protein glycosylation and lipid peroxidation, which in turn prevented abnormal activity of the enzyme in the brain. This study indicates that vitamin E supplementation may reduce complications of diabetes in the brain.
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PMID:Adenosine triphosphatase activity of streptozotocin-induced diabetic rat brain microsomes. Effect of vitamin E. 1563 22

Hyperinduced oxidant stress may have a role in the pathogenesis of diabetes and its micro- and macrovascular complications. Attaining euglycemia and the use of antioxidant vitamins could reduce oxidant stress and complications. In general, evidence does not support the use of supplements, and supplements are not recommended unless patients are deficient. Use of vitamins in excess may have adverse effects. Vitamin supplements are indicated in patients deficient in vitamins due to inadequate dietary intake or intestinal disease. Treatment with proper amounts of vitamins and antioxidants is best accomplished with a balanced diet including 3 servings of vegetables and 2 servings of fruits. Regarding supplementation of specific vitamins: carotene cannot be recommended in view of the possible harm and lack of benefit in clinical studies. Vitamin A (retinol) and Vitamin D should be repleted if deficient by laboratory assay. Excesses should be avoided. Vitamin A supplements, particularly in pregnancy, should not exceed 10,000 IU daily or a supplement should not exceed 25,000 units weekly. Vitamin E (alpha-tocopherol) alone in doses of 400 units is of questionable value, and larger doses may cause intracranial hemorrhage or interact negatively with lipid-lowering drugs. Vitamin E should not be used in patients who have bleeding disorders or patients on anticoagulants or acetylsalicylic acid (ASA). Vitamin C (ascorbic acid) losses in urine may be excessive in diabetic patients and may require repletion to 200 mg in nonsmokers and 250 mg in smokers. Further studies are needed testing: (1) vitamin supplementation in subgroups of patients at high risk for specific complications using tissue-specific indicators of oxidative stress; (2) the role of oxidative stress in nephropathy, diabetic myocardiopathy, dermopathy, joint limitation syndromes, peripheral edema, metabolic bone disease, and pregnancy; (3) the impact of renal failure on oxidative stress; and (4) the effects of diabetes and dietary vitamins on the relative amounts of retinoids, carotenoids, and vitamin E in the chylomicron and lipoproteins, and how this affects assimilation, oxidation of lipids, and atherosclerotic plaque formation.
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PMID:Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications. 1564 9

The recommended dose of Vitamin E in human pregnancy is 22-30 mg/day. High doses of Vitamin E (>or=400 IU/day) have been shown to attenuate or even prevent the damaging effect of ethanol and diabetes on the fetus in experimental animal models. The Motherisk program prospectively enrolled, and followed-up on, 82 pregnant women exposed to high doses (>or=400 IU/day) of Vitamin E during the first trimester of pregnancy. Pregnancy outcome was compared to a matched control group. The study group (n=82) was exposed to Vitamin E at doses ranging from 400-1200 IU/day. There was one pregnancy with major malformation (omphalocele) in study group. There was an apparent decrease in mean birth weight (3173+/-467 g) in Vitamin E group as compare to control (3417+/-565 g; P=0.0015); however, there were no significant differences in rates of live births, preterm deliveries, miscarriages and stillbirths. Therefore, it is concluded that consumption of high doses of Vitamin E during the first trimester of pregnancy does not appear to be associated with an increased risk for major malformations, but may be associated with decrease in birth weight.
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PMID:Pregnancy outcome following high doses of Vitamin E supplementation. 1580 90

Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
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PMID:Metals, toxicity and oxidative stress. 1589 31

Human serum paraoxonase (PON1) has been implicated to play an important role in cardiovascular disease and diabetes. Studies in the literature indicate that PON1 has two different enzyme activities, i.e., esterase and hydroperoxide reducing activities. The objective of this study was to establish the importance of these two activities and to distinguish between them. As the addition of copper immediately inactivated the enzyme, we used auto-oxidation as the model system. Auto-oxidation of HDL resulted in more than 80% reduction of the esterolytic activity, which was protected by antioxidants, Vitamin E (50%) and PDTC (95%) and completely by 1 M glucose. In contrast, the hydroperoxide reducing activity, using unesterified hydroperoxides remained unaffected with time. We also used pNPHPODE (novel substrate) to establish that hydrolysis might be a prerequisite for the enzyme to act on the esterified hydroperoxide. The results indicated that the hydrolysis of the substrate was inhibited under oxidizing conditions with no reduction of the hydroperoxide. Overall, our findings suggest that protecting the esterolytic activity of PON1 by antioxidants might be important in preserving its action on phospholipid peroxides and a concerted reaction involving the esterolytic and hydroperoxide reducing activities might be suggested for the action of PON1.
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PMID:Oxidative inactivation of paraoxonase--implications in diabetes mellitus and atherosclerosis. 1611 60

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.
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PMID:The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences. 1611 72


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