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

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
 ...
PMID:The role of free radicals in disease. 761 52

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
 ...
PMID:alpha-Lipoic acid as a biological antioxidant. 764 94

We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-beta II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta II protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [3H]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increases in total DAG and [3H]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway. 765 41

Using a precise technique for measuring authentic plasma lipid hydroperoxides (ROOHs), we show that individuals with non-insulin-dependent diabetes mellitus (NIDDM) have higher levels of ROOH than do control subjects. ROOHs were measured by the ferrous oxidation with xylenol orange assay coupled with the selective ROOH reductant triphenylphosphine. Formation of the ferric xylenol orange complex was determined at 560 nm and calibrated against H2O2. For 22 individuals with NIDDM, a concentration of 9.04 +/- 4.3 mumol/l (mean +/- SD) ROOH was recorded. This concentration was higher (P < 0.0005 by separate-variance t test) than that of plasma ROOHs from control subjects (3.76 +/- 2.48 mumol/l). There was no difference between concentrations of plasma malondialdehyde measured as thiobarbituric acid-reactive material (TBARM) in NIDDM or control subjects (1.00 +/- 0.70 vs. 1.21 +/- 0.62 mumol/l, respectively; P > 0.1). A trend to lower vitamin E levels in the NIDDM group (9.03 +/- 3.31 vs. 10.31 +/- 5.02 micrograms/ml in control subjects) failed to achieve significance at the 95% confidence level. Plasma ROOHs in the diabetic group did not correlate with total plasma cholesterol, triglyceride, fasting glucose, HbA1, vitamin E, or TBARM levels. These data indicate that measurement of authentic ROOHs shows NIDDM to be associated with oxidative stress, which may be unrelated to abnormalities in lipid metabolism and glycemic control.
Diabetes 1995 Sep
PMID:Elevated levels of authentic plasma hydroperoxides in NIDDM. 765 28

Diabetic patients develop cardiomyopathy characterized mainly by left ventricular contractile dysfunction and congestive heart failure. This study has investigated the effects of diabetes and insulin treatment on lipid peroxidation, vitamin E, and vitamin E-quinone levels in the heart ventricles of rat made diabetic by streptozotocin treatment. Controls were injected with buffer alone; a subgroup of diabetic rats were injected daily with insulin for 2 months. Membrane lipid peroxidation was measured by determining the thiobarbituric acid (TBA)-reactivity. Vitamin E and vitamin E-quinone were measured by using the high pressure liquid chromatography. There was a significant (p < 0.02) increase in the vitamin E-quinone in the heart ventricles of diabetic rats (0.33 +/- 0.05 microgram/mg phospholipid) compared with control rats (0.19 +/- 0.02). This increase was prevented in insulin-treated diabetic rats (0.20 +/- 0.03). Vitamin E levels were higher (14.15 +/- 1.17 micrograms/mg phospholipid) in diabetic rats compared to control rats (9.93 +/- 1.29 (p < 0.03). However, insulin treatment to diabetic rats did not cause any change in vitamin E levels (11.75 +/- 1.02) compared with diabetic rats. TBA reactivity was higher in the heart ventricles of diabetic rats (1.09 +/- 0.11 nmole/mg phospholipid) compared with controls (0.78 +/- 0.08, p < 0.04). Insulin treatment to diabetic rats prevented the increase in the lipid peroxidation (0.79 +/- 0.07); there were no statistically significant differences in TBA-reactivity levels in heart ventricles of insulin-treated diabetic and control rats. This study documents accumulation of vitamin E-quinone and lipid peroxidation products in heart ventricles in diabetic rats, which may have a role in the altered contractile property of the heart ventricles in diabetes.
 ...
PMID:Elevated lipid peroxidation and vitamin E-quinone levels in heart ventricles of streptozotocin-treated diabetic rats. 774 18

The specific activities of superoxide dismutase, catalase, and glutathione S-transferase (mu subtype) were significantly lower in the brains of mice with type II diabetes than in the brains of control mice. On the other hand, the specific activity of glutathione peroxidase was unaltered. The concentration of vitamin E, but not that of total glutathione and ascorbate, was increased in the brains of the type II diabetic mice. The relative amount of polyunsaturated fatty acids (as determined with soybean lipoxygenase) was increased in whole brains and crude synaptosomal membranes of the type II diabetic mice. Endogenous levels of thiobarbituric acid-positive material were decreased in both whole brain homogenates and crude synaptosomal membranes of the db/db mice. Susceptibility of lipids within whole brain homogenates and crude synaptosomal membranes of mice with type II diabetes to peroxidation with iron/ascorbate was also markedly decreased compared with that of controls. Vitamin E is known to quench lipid peroxidation. Therefore, decreased lipid peroxidation in the type II mouse brain may be due to increased vitamin E content.
 ...
PMID:Antioxidant defense systems in the brains of type II diabetic mice. 779 Aug 73

Thirty six individuals with angiographic evidence of coronary atherosclerosis and thirty six individuals without coronary disease, matched for a variety of cardiovascular risk factors including age, sex, smoking, hypertension, diabetes and family history, were evaluated for their serum concentrations of vitamin E, total cholesterol, triacylglycerols, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, apolipoprotein A-I, and apolipoprotein B. Apolipoprotein B, low density lipoprotein-cholesterol and total cholesterol concentrations were unequivocally higher in patients with coronary artery disease. Triacylglycerols were marginally higher in patients with disease. The antioxidant vitamin E (alpha-tocopherol) was significantly higher in patients with atherosclerosis when compared with controls (35.1 +/- 17.0 mumol/l vs. 29.0 +/- 13.2 mumol/l, p = 0.017). However, alpha-tocopherol concentrations were strongly associated with lipid concentrations and normalization to the total cholesterol concentrations produced ratios which were not significantly different in the two groups. Logistic regression analysis revealed that the association of lipid risk factors with coronary stenosis was determined primarily by the difference in total cholesterol values. This study demonstrated that in this group of patients referred for angiography and matched for other risk factors, higher alpha-tocopherol concentrations were associated with patients with coronary disease and were not useful for assessing risk of coronary artery disease.
 ...
PMID:Vitamin E compared with other potential risk factor concentrations in patients with and without coronary artery disease: a case-matched study. 781 29

Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.
 ...
PMID:Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats. 782 6

The prevalence of coronary artery (CAD) disease in the Indian urban population is comparable to British population. Dietary intakes, antioxidant vitamins, prevalence of risk factors and CAD, were studied in a random sample of 152 adult urban subjects between 26-65 years of age (80 males, 72 females) from Peerzada street, Moradabad and compared with Indian immigrants to U.K. and a British comparison group. There was no significant relation with vitamin A. Smoking and diabetes were the confounding factors. Plasma antioxidant vitamin C (21.6 +/- 3.3 vs 42.5 +/- 4.5 mumol/L), vitamin E (15.2 +/- 2.8 vs 21.4 +/- 3.2 mumol/L) and beta-carotene (0.33 +/- 0.6 vs 0.55 +/- 0.08 mumol/L) were significantly lowered and lipid peroxides higher (2.82 +/- 0.22 vs 1.3 +/- 0.20 nmol/ml) in patients with CAD compared to subjects without any risk factors. The relation between low plasma level of vitamin C and E levels and carotene remained independently and inversely related after adjustment for smoking, diabetes and other risk factors. Regression analysis showed that after adjustment. Odd's ratio for carotene (1.82, 95% C.I. 0.50 to 3.72), vitamin C (2.23, 95% C.I. 1.14 to 5.26) and vitamin E (2.35, 95% C.I. 1.29 to 5.30) were significantly related to CAD. Underlying these changes, dietary intake of vitamin A, E, C and beta-carotene was significantly less in patients with CAD. Vitamin C and beta-carotene intake were less in smokers and diabetes. Compared with British population, the Indian urbans consumed less total and saturated fat and cholesterol and more polyunsaturated fat and complex carbohydrates. The plasma total and low density lipoprotein cholesterol levels were less in Indian urbans compared to Britons and so were mean body weight, body mass index and waist-hip ratio. Plasma insulin levels were comparable. The fatty acid composition of the diet, blood lipids, central obesity and insulin levels do not appear to account for high rates of CAD among Indians. The findings suggest that urban population in India may benefit from eating diets rich in antioxidant vitamin C, E and beta-carotene.
 ...
PMID:Diet, antioxidant vitamins, oxidative stress and risk of coronary artery disease: the Peerzada Prospective Study. 783 64

Vitamin E was administered to non-obese diabetic (NOD) mice to determine if the selective destruction of pancreatic beta cells leading to Type 1 (insulin dependent) diabetes mellitus could be halted by virtue of this vitamin's free oxygen radical scavenger activity. Two groups of NOD mice were treated from 3 weeks of age until 30 weeks of age with either diet supplemented with vitamin E or control diet. Diabetes incidence was recorded as well as the degree of lymphocytic infiltration of the pancreas (insulitis) in animals which did not develop diabetes. Vitamin E did not reduce the incidence of diabetes by 30 weeks of age, however it did significantly delay the onset of the disease (p < 0.01--parallelism test). There were no differences in the degree of insulitis with respect to control mice. We conclude that antioxidant therapy with Vitamin E delays diabetes onset in NOD mice without having an apparent effect on the autoimmune process.
 ...
PMID:Vitamin E delays diabetes onset in the non-obese diabetic mouse. 785 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>