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

The tissue concentration of lipid hydroperoxides, which was determined by a specific method involving chemical derivatization and HPLC, increased significantly in the heart, liver, kidney and muscle of diabetic rats 8 weeks after the intraperitoneal injection of streptozotocin compared with that of the control group. These results demonstrate that an enhanced oxidative stress is caused in these tissues by diabetes. Vitamin C concentrations of the brain, heart, lung, liver, kidney and plasma of the diabetic rats decreased significantly after 8 weeks compared with those of the control group. Vitamin E concentrations of the brain, heart, liver, kidney, muscle and plasma of the diabetic rats increased significantly after 4 weeks compared with the control group. After 8 weeks, an elevation in vitamin E concentration was observed in the heart, liver, muscle and plasma of the diabetic rats.
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PMID:Change in tissue concentrations of lipid hydroperoxides, vitamin C and vitamin E in rats with streptozotocin-induced diabetes. 991 99

Insulin resistance of skeletal muscle is fundamental to both syndrome X and its frequent sequel, type II diabetes. In these disorders, excessive exposure of muscle to free fatty acids (FFAs) and their metabolic derivatives appears to play a prominent role in the induction of insulin resistance. Recent evidence suggests that activation of novel isoforms of protein kinase C (PKC) by diacylglycerol may mediate at least part of the adverse impact of FFAs on muscle insulin sensitivity. Vitamin E and fish oil omega-3s, by promoting the activity of diacylglycerol kinase and inhibiting that of phosphatidate phosphohydrolase, should reduce diacylglycerol levels, thus accounting for their documented favorable impact on insulin sensitivity. Thiazolidinediones such as troglitazone, on the other hand, appear to intervene in the signaling pathway whereby PKC down-regulates insulin function. The insulin-sensitizing activity of chromium picolinate may be attributable, at least in part, to increased expression of insulin receptors. In combination with lifestyle modifications which reduce FFA exposure--weight loss, very-low-fat eating, excessive training--these measures can be expected to work in a complementary way to promote increased numbers of insulin receptors that are more functionally competent. As these measures appear to be safe and well-tolerated, they may have utility for the prevention of diabetes as well as its therapy. When they do not prove sufficient to achieve optimal glycemic control, excessive hepatic glucose output and impaired cell response to glucose can be addressed with metformin and sulfonylureas, respectively. The prospects for a rational medical management of type II diabetes, obviating the need for injectible insulin, have never been brighter.
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PMID:Complementary measures for promoting insulin sensitivity in skeletal muscle. 1005 64

Impaired antioxidant defence is implicated in the development of cardiovascular complications in non-insulin-dependent diabetes (NIDDM). However, as many of these patients are elderly, observed changes in antioxidant status may be due to the patient's age rather than their disease. We sampled blood from 47 elderly NIDDM patients (21 male and 26 female; mean age +/- SD, 75.62 +/- 7.97 years), 66 young (30 male and 36 female; 24.52 +/- 4.72 years) and 58 healthy elderly volunteers (17 male and 41 female; 70.74 +/- 4.85 years), and measured the antioxidant glutathione, the marker for free-radical-damage lipid hydroperoxide products (LHP), vitamin E and total antioxidant capacity (TAC). There was a significant increase in LHP in the healthy elderly group compared with the young volunteers (3.14 +/- 1.5 vs. 2.14 +/- 1.38 mumol/l, p < 0.01). The values were much higher in NIDDM patients (7.02 +/- 2.29 mumol/l, p < 0.0001 vs. healthy elderly). There was a reduction in TAC in healthy elderly compared with the young (359.99 +/- 54.82 vs. 471.47 +/- 94.29 mumol/l trolox equivalents, p < 0.0001), but there was no further reduction in NIDDM patients. Similarly, glutathione was reduced to the same degree in healthy elderly and NIDDM patients (0.29 +/- 0.09, 0.30 +/- 0.11 vs. 0.54 +/- 0.19 mumol/l in young volunteers, p < 0.0001). Vitamin E concentrations were comparable in all groups (26.34 +/- 5.39 young volunteers, 31.50 +/- 8.23 healthy elderly and 30.98 +/- 9.03 mumol/l NIDDM patients), but after correction for serum cholesterol there was a significant reduction in the diabetic group compared with the young, but not with the elderly (5.54 +/- 1.55 vs. 6.67 +/- 1.86 vs. 6.31 +/- 1.85 (mumol/l)/(mmol/l), p < 0.01). We have demonstrated an age-dependent reduction in total antioxidant capacity and glutathione defence and an age-independent increase in LHP in elderly patients with NIDDM. Reduced concentrations of vitamin E were demonstrated in NIDDM patients compared with young, but not elderly, volunteers. Increased oxidative damage occurs independently of age in NIDDM patients despite comparable antioxidant defences in this age group.
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PMID:Age-independent oxidative stress in elderly patients with non-insulin-dependent diabetes mellitus. 1020 70

Vitamin E is considered to be one of the most important antioxidants. There is a trend today to supply diabetic children with vitamin E in order to prevent microvascular complications. In this study, our objective was to demonstrate validity of plasma and erythrocyte vitamin E levels in diabetic children. This study was conducted on twenty-five diabetic patients aged from 7-16 years and ten non-diabetic, age-matched healthy subjects as the control group. Vitamin E levels were measured by high-performance liquid chromatography. There was no significant difference between the mean plasma vitamin E levels of diabetic and control groups, 870.80 +/- 220.51 micrograms/dl and 891 +/- 221.21 micrograms/dl, respectively (p > 0.05). The mean erythrocyte vitamin E levels of diabetic and control groups were significantly different: 183.12 +/- 62.58 micrograms/dl and 246.90 +/- 68.26 micrograms/dl, respectively (p < 0.05). Erythrocyte vitamin E levels were significantly lower than plasma vitamin E levels in both groups. We further investigated whether a correlation exists between plasma and erythrocyte vitamin E levels and duration of diabetes, insulin dose and HbA1c measurements. However no correlation was found. In conclusion, measurement of erythrocyte vitamin E levels may be considered to be more valuable than plasma vitamin E levels in diabetic children and supplementation may be provided according to erythrocyte levels rather than plasma levels.
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PMID:Plasma and erythrocyte vitamin E levels in children with insulin dependent diabetes mellitus. 1039 66

Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway. The major source of DAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the beta-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes--such as a decrease in the activity of Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation--are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531, a selective PKC-beta-isoform inhibitor, and d-alpha-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that DAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the DAG-PKC pathway in developing vascular complications in diabetic patients.
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PMID:The role of protein kinase C activation in the pathogenesis of diabetic vascular complications. 1040 23

Increased oxidative stress, hypofibrinolysis and insulin resistance are present in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radical production, but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action examined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxidative stress and fibrinolysis were also determined. The administration of vitamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 +/- 7.5 micromol/kg/min, P < 0.02) and of metabolic clearance rate of glucose (3.7 +/- 1.6 vs 2.9 +/- 0.8 ml/kg/min. P < 0.02). A decrease of insulin receptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 171 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MDA) concentration documented an increased oxidative stress in diabetic patients as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 micromol/l, P<0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = -0.73). Vitamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PAI-1. In conclusion. our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 diabetic patients.
Diabetes Res Clin Pract 1999 Apr
PMID:Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus. 1041 37

Oxidative stress has been proposed to play a role in many disease states, including cardiovascular and infectious diseases, cancer, diabetes and neurodegenerative pathologies. The fact that these diseases have an increased incidence in uremia, and particularly in dialysis patients, suggests an increased exposure to oxidative stress in this condition. In haemodialysis (HD), the absence of a complete correction of the uremic toxicity together with the untoward effects of the dialysis, malnutrition and the progressive worsening of the clinical condition, can lead to a high susceptibility to oxidative stress by an abnormal production of oxidants - including reactive oxygen species (ROS) and uremic toxins with prooxidant function - and defective antioxidant protection. One of the most investigated biological effects of the oxidative stress in the HD patients is lipid peroxidation in plasma and blood cell membranes. Moreover, we have recently described how abnormal apoptosis in peripheral blood leukocytes is associated with cell oxidative stress (intracellular thiol depletion). Vitamin E, in both in vitro and in vivo conditions, has been proposed to partially correct these effects. In this review we evaluated some features of two new dialysis strategies using an antioxidant approach to the protection against the oxidant stress in HD. Their rationale is based on the emerging role of vitamin E in counteracting some biological effects associated with oxidant stress namely lipid peroxidation and apoptosis. These techniques use: 1) the recirculation of the dialysate through a suspension of vitamin E-enriched liposomes combined with the supplementation by the dialysate with ascorbic acid, this method has been called hemolipodialysis; 2) the coating of the dialysis membrane with vitamin E (vitamin E- modified dialysis membranes). These unconventional approaches to the antioxidant therapy in HD open a widely unexplored and promising field in the evolution of the biomaterials and dialysis quality.
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PMID:Biological effects of oxidant stress in haemodialysis: the possible roles of vitamin E. 1044 65

Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Glutathione, another natural antioxidant, may also be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus. Our group has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium levels (Mg([i])). Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions. To directly investigate the effects of vitamin E supplementation on insulin sensitivity in hypertension, in relation to the effects on circulating levels of reduced (GSH) and oxidized (GSSG) glutathione and on Mg([i]), we performed a 4-week, double-blind, randomized study of vitamin E administration (600 mg/d) versus placebo in 24 hypertensive patients and measured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/GSSG ratios, and Mg([i]) before and after intervention. The relationships among WBGD, GSH/GSSG, and Mg([i]) in both groups were evaluated. In hypertensive subjects, vitamin E administration significantly increased WBGD (25.56+/-0.61 to 31.75+/-0.53 micromol/kg of fat-free mass per minute; P<0.01), GSH/GSSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg([i]) (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01). In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r=0.58, P=0.047) and Mg([i]) (r=0.78, P=0.003). These data show a clinical link between vitamin E administration, cellular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further studies are needed to explore the cellular mechanism(s) of this association.
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PMID:Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. 1052 98

Lipid deposits, foam cell collection and accumulation of mesangial matrix components are recognized as early events in the development of focal segmental glomerulosclerosis (FSGS). Studies have suggested that oxidative stress is increased in uremic patients. Oxidized low-density lipoprotein (Ox-LDL) has been identified in the lesions of FSGS. Dietary antioxidants reduced not only the staining intensity of Ox-LDL but also the severity of renal injury in rats with experimental FSGS possibly by making lipoproteins resistant to oxidation. In vitro studies showed that LDL during its incubation with human mesangial cells (HMC) was peroxidatively modified and stimulated alpha1(I), alpha1(III), and alpha1(IV) collagen mRNA expression. Vitamin E, an antioxidant, and antibody against Ox-LDL caused a marked reduction in collagen mRNA stimulated by LDL. These findings suggest that LDL deposited and oxidized in the glomeruli may be implicated in the development of glomerulosclerosis by facilitating excessive mesangial matrix generation.
Diabetes Res Clin Pract 1999 Sep
PMID:Oxidized LDL, glomerular mesangial cells and collagen. 1058 63

We have reported that d-alpha-tocopherol can prevent hyperglycemia-induced activation of DAG and PKC levels in vascular tissues as well as normalizing retinal blood flow and renal hyperfiltration. The mechanism of this effect, however, is not clear. Aside from alpha-tocopherol's principal role as an antioxidant agent, it has also been shown to act as a membrane stabilizer. Another possibility is that the effect of alpha-tocopherol is focused on the activation of DAG kinase, which is a key enzyme in the metabolism of DAG. Therefore, in this study, we examined the effect of alpha-tocopherol on the DAG kinase activity in vascular smooth muscle cell. We have also examined the effect of alpha-tocopherol, its analogues, and probucol on DAG kinase activities and expression. The present study showed that d-alpha-tocopherol's inhibitory effect on DAG-PKC pathway is by increasing DAG kinase activity in rat and human vascular smooth muscle cell (VSMC). Total DAG level was increased by 40 +/- 10% (mean +/- S.E.) (P < 0.05) in human VSMC, after exposure to 22 vs 5 mM glucose. This increase was normalized by d-alpha-tocopherol treatment in a concentration-dependent manner. In parallel, DAG kinase activation by d-alpha-tocopherol was also induced in a time- and dose-dependent manner. DAG kinase activity was increased by 57 +/- 19% (P < 0.05) in human VSMC and 112 +/- 35% (P < 0.05) in rat VSMC after 24 h of incubation with d-alpha-tocopherol (100 microg/ml). Another lipophilic antioxidant, probucol, also increased DAG kinase activity by 124 +/- 34%, but other vitamin E analogues with much less antioxidant potencies were ineffective. Western blots of various DAG kinase isoforms were not changed by d-alpha-tocopherol treatment. These results provide strong and detailed evidence that d-alpha-tocopherol can prevent hyperglycemia induced DAG-PKC activation by enhancing DAG kinase activity, probably through an antioxidant effect.
Diabetes Res Clin Pract 1999 Sep
PMID:d-Alpha-tocopherol prevents the hyperglycemia induced activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular smooth muscle cell by an increase of DAG kinase activity. 1058 71


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