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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gerbil Psammomys obesus develops nutrition-dependent diabetes associated with moderate obesity. The disease is characterized by initial hyperinsulinemia, progressing to hypoinsulinemia associated with depleted pancreatic insulin stores. The contribution of changes in beta-cell turnover to insulin deficiency was investigated in vivo during transition to overt diabetes. Normo glycemic diabetes-prone P. obesus animals who were given a high-calorie diet developed hyperglycemia within 4 days, which was found to be associated with a progressive decline in pancreatic insulin content. This was accompanied by a transient increase in beta-cell proliferative activity and by a prolonged increase in the rate of beta-cell death, culminating in disruption of islet architecture. The hypothesis that "glucotoxicity" was responsible for these in vivo changes was investigated in vitro in primary islet cultures. Exposure of islets from diabetes-prone P. obesus to high glucose levels resulted in a dose-dependent increase in beta-cell DNA fragmentation. In contrast, high glucose levels did not induce DNA fragmentation in rat islets, whereas islets from a diabetes-resistant P. obesus line exhibited a reduced and delayed response. Aminoguanidine did not prevent glucose-induced beta-cell DNA fragmentation in vitro, suggesting that formation of nitric oxide and/or advanced glycation end products plays no major role. Elevated glucose concentrations stimulated beta-cell proliferation in both rat and P. obesus islets. However, unlike the marked long-lasting effect in rat islets, only a transient and reduced proliferative response was observed in P. obesus islets; furthermore, beta-cell proliferation was inhibited after prolonged exposure to elevated glucose levels. These results suggest that hyperglycemia-induced beta-cell death coupled with reduced proliferative capacity may contribute to the insulin deficiency and deterioration of glucose homeostasis in P. obesus. Similar adverse effects of hyperglycemia could play a role in the evolution of type 2 diabetes in genetically susceptible individuals.
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PMID:Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. 1010 89

Endothelial dysfunction appears to be an integral aspect of the insulin resistance syndrome, independently of hyperglycemia. The ability of insulin to cause endothelium-derived nitric oxide (NO)-dependent vasodilation amplifies its overall effect of stimulating skeletal muscle glucose uptake and modulating vascular tone. The dose-dependent physiologic increase in skeletal muscle blood flow in response to insulin, which is highly associated with the rate of glucose metabolism, is impaired in insulin-resistant states. Insulin appears to mediate vasodilation by direct stimulation of release of NO from endothelium. Studies of the response to the endothelium-dependent vasodilator methacholine chloride in lean and obese nondiabetic subjects and obese subjects with type 2 diabetes mellitus indicate that there may be marked endothelial dysfunction very early in insulin resistance. The potent vasoprotective effects of NO mitigate various atherogenic processes, including vascular smooth muscle cell proliferation, platelet adhesion and thrombogenesis, lipid peroxidation, and monocyte adhesion to endothelial cells. The interaction between insulin and NO may contribute to the prominent outcomes of insulin resistance syndrome (viz., hypertension, thrombosis, and atherosclerosis).
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PMID:Vascular reactivity. 1041 55

Atherosclerotic macrovascular disease is the leading cause of both morbidity and mortality in non-insulin dependent diabetes mellitus. Endothelial dysfunction is a key, early and potentially reversible event in pathogenesis of atherosclerosis. Its occurrence in non-insulin dependent diabetes mellitus is well supported by both in-vitro and in-vivo studies. Non-insulin dependent diabetes mellitus results in diverse abnormalities of lipid and lipoprotein metabolism, in particular hypertriglyceridaemia, low levels of high density lipoprotein and abnormalities of post-prandial lipaemia. A variety of studies demonstrate the presence of enhanced oxidative stress in non-insulin dependent diabetes mellitus, with recent data implying an association between oxidative stress, post-prandial lipaemia and endothelial dysfunction in non-diabetic subjects. In this article based on in-vitro and human studies, we develop the hypothesis that endothelial dysfunction in non-insulin dependent diabetes mellitus is the consequence of the diabetic dyslipidaemia, in particular post-prandial lipaemia, and of oxidative stress on the action of nitric oxide. The practical applications of this theory provide potential therapeutic options which may reduce the risk of vascular disease in non-insulin dependent diabetes mellitus.
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PMID:Diabetic dyslipidaemia and coronary heart disease: new perspectives. 1055

A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, n=9) or type 2 diabetes (D, n=9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N(G)-monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as mean+/-SE MCR (mL/kg per minute) were 7.22+/-0. 99 (C), 6.32+/-0.78 (H), and 5.06+/-0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1+/-5.6% (C), 17. 2+/-5.5% (H), and 12.3+/-6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9+/-5.1% (C), 37.5+/-2.3% (H), and 33.6+/-2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (r=0. 46, P<0.05), MCR and LNV (r=0.44, P<0.05), and IGMV and LNV (r=0.52, P<0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans.
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PMID:Insulin action is associated with endothelial function in hypertension and type 2 diabetes. 1064 50

Production of the superoxide radical anion O2-. and the nitric oxide radical NO-. by granulocytes was studied in 14 patients with type 2 diabetes without nephropathy, 21 patients with type 2 diabetes and diabetic nephropathy, and 19 healthy subjects, both without and after stimulation with opsonized zymosan. O2-. production by both resting and stimulated granulocytes was increased in type 2 diabetes patients without nephropathy but decreased in type 2 diabetes patients with nephropathy, compared with healthy subjects. NO. generation was highly augmented in type 2 diabetes patients without nephropathy by both resting and stimulated cells; values for type 2 diabetes patients with nephropathy were intermediate between the type 2 diabetes patients without nephropathy and the healthy subjects. These data point to granulocytes as one of possible sources of oxidative stress in type 2 diabetes.
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PMID:Production of superoxide and nitric oxide by granulocytes in non-insulin-dependent diabetic patients with and without diabetic nephropathy. 1069 Jun 52

Several studies have shown that the activities of delta-6-desaturase and delta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II diabetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, especially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But, no information is available as to the relationship between L-arginine-nitric oxide system and the metabolism of essential fatty acids in diabetes mellitus. In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated group; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increase in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. Further, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism. The abnormalities in the essential fatty acid metabolism observed also reverted to normalcy following control of diabetes with insulin. These results indicate that nitric oxide can enhance the activities of delta-6- and delta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metabolism of essential fatty acids.
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PMID:Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. 1076 77

Type 2 diabetes is characterized by impaired endothelial dependent vasodilatation which may contribute to the high prevalence of vascular disease in such patients. Although hyperglycaemia, dyslipidaemia and hypertension can all independently cause a similar defect, recent data suggest that endothelial dysfunction may be intrinsic to the insulin resistance syndrome that commonly precedes type 2 diabetes. Such abnormalities in endothelial function could represent the impact of subclinical disturbance of metabolism or alternatively the presence of a common cellular defect that influences both nitric oxide bioavailability and insulin mediated glucose disposal. Resolution of this puzzle is likely to lead to important advances in our knowledge and ultimately treatment of vascular disease.
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PMID:Adverse endothelial function and the insulin resistance syndrome. 1079 55

We studied the possible relationship between nitric oxide (NO) production and insulin resistance in patients with type 2 diabetes mellitus. Urine NO metabolites (NOx) were measured as an index for NO production by HPLC combined with a Cd column, Griess reaction and a spectrophotometer in 403 healthy control subjects and 102 hospitalized patients with type 2 diabetes. Glucose infusion rate (GIR) was measured as a reverse index for insulin resistance by euglycemic glucose clamp study using an artificial pancreas in 20 of 102 diabetic patients. Urine NOx was lower in the patients with type 2 diabetes than in healthy control subjects (mean+/-SE: 3.18 +/-0.02 versus 3.25 +/-0.01 log[-micromol/gCr], p<0.01). Urine NOx was correlated with body mass index (BMI) in 102 diabetic patients (r= -0.372, p<0.001), but not related to either age, sex, fasting plasma glucose, HbA1c or blood pressure. Urine NOx was correlated with GIR independent of BMI in 20 diabetic patients (r=0.774, P<0.0001). These findings suggest that NO production is closely related with insulin resistance in patients with type 2 diabetes.
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PMID:Reverse correlation between urine nitric oxide metabolites and insulin resistance in patients with type 2 diabetes mellitus. 1081 Dec 96

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(-1)/pmol/L) x 10(3)] was significantly greater in those without a family history (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.
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PMID:Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes. 1090 87

We have recently made the novel observation that a pro-oxidant challenge with hydroquinone in combination with buthionine sulfoximine (each at 50 mg/kg i.p. daily for 7 days) provokes the onset of type II diabetes mellitus in a model of insulin resistance, the obese Zucker rat. Since endothelial dysfunction in oxidant stress may aggravate in vivo insulin resistance, we have now investigated endothelium-dependent and nitric oxide (NO)-mediated vascular responses in the obese Zucker rat in vivo following this pro-oxidant insult. Pro-oxidant-treated animals exhibited defective vasodepression to the endothelium-dependent agent acetylcholine and to a lesser extent, the NO donor glyceryl trinitrate, together with a reduction in circulating levels of cGMP. Our data therefore suggest that the progression to type II diabetes mellitus in the obese Zucker rat mediated by a pro-oxidant insult is associated with impairments in agonist-stimulated, endothelium-dependent vasodilation and vascular NO signalling.
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PMID:Endothelial dysfunction accompanies a pro-oxidant, pro-diabetic challenge in the insulin resistant, obese Zucker rat in vivo. 1094 Mar 62


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