Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Observational studies with healthy persons demonstrated an inverse association of vitamin E with the risk of coronary heart disease or cancer, the outcome of large-scale clinical trials conducted to prove a benefit of vitamin E in the recurrence and/or progression of such disease, however, was disappointing. Vitamin E did not provide benefits to patients with cardiovascular diseases, cancer, diabetes or hypertension. Even harmful events and worsening of pre-existing diseases were reported, which are hard to explain. Since vitamin E is metabolized along the same routes as xenobiotics and induces drug-metabolizing enzymes in rodents, it is hypothesized that a supplementation with high dosages of vitamin E may also lead to an induction of the drug-metabolizing system in patients that depend on drug therapy. Compromising essential therapy might therefore outweigh any benefit of vitamin E in patients. It is recommended to work out at which threshold the drug-metabolizing system can be induced in humans before new trials with high dosages of vitamin E are started.
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PMID:Adverse effects of vitamin E by induction of drug metabolism. 1885 Jan 80

The effect of vitamin E (1 g/kg body weight) supplementation on myosin-V and neuronal nitric oxide synthase (nNOS) immunoreactive myenteric neurons from the ileum of diabetic rats was investigated in the present study. Forty animals were divided into the following groups: normoglycemics (N), normoglycemics treated with vitamin E (NE), diabetics (D), and diabetics treated with vitamin E (DE). Quantitative and morphometric analyses were performed. The area of the tertiary plexus was also determined. Diabetes produced a 24% reduction in the number of myosin-V neurons in group D compared with group N, an effect that was accompanied by an increase in the tertiary plexus area (P < 0.05). Neuronal density was 27% higher in group NE than group N (P < 0.05). Nitrergic neuronal density was not altered as a consequence of either diabetes or vitamin E treatment. Myosin-V and nNOS immunoreactive neuronal cell body area increased significantly in group NE. The area of myosin-V and nNOS myenteric neurons also increased in group D. Vitamin E treatment (group DE) increased only the size of nitrergic neurons. The present results suggest that vitamin E elicited a neuroprotective and neurotrophic effect on the natural aging process, but with regard to diabetes, vitamin E supplementation exerted a neurotrophic effect only on nitrergic neurons.
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PMID:Vitamin E supplementation in rats with experimental diabetes mellitus: analysis of myosin-V and nNOS immunoreactive myenteric neurons from terminal ileum. 1895 59

The role of nutritional supplementation is of increasing interest with regard to ocular disease. Randomised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration, and formulations are now being developed for use by people with diabetes and diabetic retinopathy. The aim of this review was to synthesise the evidence for use of nutritional supplementation in type 2 diabetes. MEDLINE and EMBASE databases were searched using a systematic approach. Only double-masked randomised controlled trials were selected. A total of 50 trials were identified as suitable for inclusion. The potential role of alpha-lipoic acid, chromium, folic acid, isoflavones, magnesium, Pycnogenol, selenium, vitamin C, vitamin E, and zinc in the treatment of type 2 diabetes is discussed. The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors. Chromium was the most studied supplement, accounting for 16 of the 50 trials. A majority of the trials found a positive effect of chromium on fasting plasma glucose. Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures, but only when combined with soy proteins. Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1) or more.
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PMID:Nutritional supplementation for type 2 diabetes: a systematic review. 1907 53

Polymorphic loci regulating oxidative stress are potential susceptibility genes for diabetic nephropathy (DN). Haptoglobin (Hp) is an antioxidant protein which serves to protect against oxidative stress induced by extracorpuscular hemoglobin. There are two alleles at the Hp locus, 1 and 2. The Hp 1 protein is a superior antioxidant to the Hp 2 protein. The Hp 2 allele has been associated with increased prevalence of DN and appears to be associated with a more rapid progression to end-stage renal disease. We sought to recapitulate this association between Hp genotype and DN in mice genetically modified at the Hp locus. We assessed morphometric, histologic, and functional parameters involved in the development and progression of DN in mice with diabetes mellitus (DM) with either the Hp 2-2 or Hp 1-1 genotype. Morphometric analysis demonstrated that glomerular and proximal tubular hypertrophy were significantly increased in Hp 2-2 DM mice. Histological analysis demonstrated that Hp 2-2 DM mice had significantly more collagen type IV, smooth muscle actin, and increased renal iron deposition. Studies of renal function demonstrated creatinine clearance time and albuminuria were increased in Hp 2-2 DM mice. Vitamin E provided significant protection against the development of functional and histological features characteristic of DN to Hp 2-2 DM but not to Hp 1-1 DM mice. These studies serve to strengthen the association between the Hp 2-2 genotype and diabetic renal disease and suggest a pharmacogenomic interaction may exist between the Hp genotype and vitamin E.
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PMID:Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus. 1917

Antioxidant therapy has been proposed to improve the oxidative stress status of diabetic patients. Natural products are a source of substances such as carotenoids, with known antioxidant properties with possible benefits on diabetes. Among them, Dunaliella salina is a microalga with high content in carotenoids that can be extracted via an environmentally clean process such as supercritical fluid extraction with CO2. Five doses of D. salina extract with in vitro antioxidant properties were intragastrically administrated to adult male streptozotocin (STZ) diabetic rats. Urine fingerprints of control and diabetic rats, both with and without treatment, were obtained by capillary electrophoresis with two different modes (normal polarity and MEKC and reverse polarity and CZE). When the profiles were submitted together to pattern recognition techniques they showed the effects of D. salina extract on this acute and short-term treatment animal model in a rapid, simple and cost-effective way without identifying a single marker. In order to have a further biochemical knowledge of the effect, after treatment, rats were sacrificed and blood and liver glutathione, as well as plasma glucose, triglycerides, cholesterol, total protein, urea, acetoacetate, 3-hydroxybutyrate, lactate, pyruvate and urate, TBARS and urine 8-isoprostane were analysed. Vitamin E in plasma and liver was also measured. Twenty-seven parameters were individually assessed, and both univariate statistics (mean comparison after 1W-ANOVA) and multivariate data analysis were performed. D. salina extract induced changes showed up by the multivariate analysis. Results of the treatment from most of the parameters can be considered beneficial for diabetic animals; although an increase in hyperglycemia and 8-isoprostane excretion when STZ treated animals received the extract was observed.
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PMID:Dunaliella salina extract effect on diabetic rats: metabolic fingerprinting and target metabolite analysis. 1923 50

Vitamin E is comprised of two classes of compounds: tocopherols and tocotrienols. Tocotrienol-enriched palm oil has been shown to help reduce blood glucose levels in patients and preclinical animal models. However, the mechanistic basis for tocotrienol action is not well established. Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are ligand-regulated transcription factors that play essential roles in energy metabolism. Importantly, synthetic PPARalpha and PPARgamma ligands are currently used for treating hyperlipidemia and diabetes. In this study, we present data that tocotrienols within palm oil functioned as PPAR modulators. Specifically, both alpha- and gamma-tocotrienol activated PPARalpha, while delta-tocotrienol activated PPARalpha, PPARgamma, and PPARdelta in reporter-based assays. Tocotrienols enhanced the interaction between the purified ligand-binding domain of PPARalpha with the receptor-interacting motif of coactivator PPARgamma coactivator-1alpha. In addition, the tocotrienol-rich fraction of palm oil improved whole body glucose utilization and insulin sensitivity of diabetic Db/Db mice by selectively regulating PPAR target genes. These lines of evidence collectively suggested that PPARs represent a set of molecular targets of tocotrienols.
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PMID:Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors. 1986 71

This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl(4) and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl(4)) (1 ml/kg/3 days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In CCl(4)-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy order was vitamin E > or = melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl(4) and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was nearly the same in CCl(4) and diabetes-induced liver damage.
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PMID:Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress. 2011 17

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ~5 fold and glucose 6-phosphate dehydrogenase activities were decreased by ~25% compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased significantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to function in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.
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PMID:Dehydroepiandrosterone supplement increases malate dehydrogenase activity and decreases NADPH-dependent antioxidant enzyme activity in rat hepatocellular carcinogenesis. 2012 70

We investigated the effects of chronic administration of vitamin E on nitric oxide (NO)-producing neurons in the brains of streptozotocin (STZ)-induced diabetic rats using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. We further evaluated the effects of diabetes and vitamin E treatment on experimental anxiety and memory processes using the elevated plus maze (EPM) Trial 1/2 protocol. Wistar rats were divided into four groups: normoglycemics (N), normoglycemics treated with vitamin E (NVE), diabetics (D), and diabetics treated with vitamin E (DVE). Diabetes mellitus was induced by a single intraperitoneal injection of STZ (35mg/kg). Vitamin E (100mg/kg) or vehicle was administered orally by gavage (1ml/kg) once each day for 7 weeks. After behavioral testing, the dentate gyrus of the hippocampus (DG), striatum, paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), and dorsolateral periaqueductal grey (DLPAG) were analyzed for NADPH-d histochemistry. STZ-induced diabetic rats exhibited decreased locomotor activity and cognitive impairment compared with normoglycemic controls. The number of NADPH-d-positive neurons was increased in the DG, striatum, and DLPAG of diabetic rats. An increase in soma area was detected in all structures analyzed (DG, striatum, PVN, SON, and DLPAG) of STZ-induced diabetic animals. The present study showed that chronic administration of vitamin E ameliorates memory in STZ-induced diabetic rats and revealed that NOS-producing neurons have an increased soma area which can be restored, at least partially, by vitamin E treatment. These results suggest the potential use of vitamin E as an adjuvant therapy for the prevention and treatment of diabetic conditions.
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PMID:Vitamin E improves learning performance and changes the expression of nitric oxide-producing neurons in the brains of diabetic rats. 2013 20

Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium-vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium-vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (p<0.01). In conclusion, vitamin E plus selenium seems to be a more potent antioxidant compared to melatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects.
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PMID:Selenium-vitamin E combination and melatonin modulates diabetes-induced blood oxidative damage and fetal outcomes in pregnant rats. 2124 May 68


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