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

Arginine metabolism via nitric oxide (NO) synthase and other pathways was studied in coronary endothelial cells (EC) from the spontaneously diabetic BB rat, an animal model of human type I diabetes mellitus (IDDM). EC were prepared from insulin-treated diabetic BB (BBd) and non-diabetes-prone BB (BBn) rats. Basal NO synthesis was studied in EC cultured for 48 h in medium containing 0.4 mM L-arginine. At the end of the culture period, the medium was analyzed for nitrite and nitrate (two major end stable oxidation products of NO), and the cells were used to determine arginine uptake and metabolism and the activities of some arginine-degrading enzymes. For studies of arginine metabolism, cells were incubated at 37 degrees C for 1 h in Krebs-Henseleit bicarbonate buffer (pH 7.4) containing 1 mM L(-)[1-14C]arginine or L(-)[1-14C]ornithine. The rates of production of nitrite plus nitrate by BBd EC were only 15% of those of BBn cells. This impaired NO synthesis in BBd EC was not due to alterations in arginine uptake, NO synthase activity, or intracellular arginine concentrations but might have resulted from a limited intracellular availability of cofactors of NO synthase. In addition to the arginine-NO pathway, arginine was found to be metabolized to urea, ornithine, and, to a much lesser extent, CO2 via arginase and ornithine aminotransferase. The activities of arginase and the formation of ornithine and urea from arginine were decreased by 90% in BBd compared with BBn cells. These results, coupled with the reduced NO synthesis, indicate metabolic defects in arginine metabolism in BBd EC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired arginine metabolism and NO synthesis in coronary endothelial cells of the spontaneously diabetic BB rat. 748 63

Normal subjects, fasted 60 h, and patients with insulin-dependent diabetes mellitus (IDDM), withdrawn from insulin and fasted overnight, were given phenylacetate orally and intravenously infused with [3-14C]lactate and 13C-bicarbonate. Rates of hepatic gluconeogenesis relative to Krebs cycle rates were estimated from the 14C distribution in glutamate from urinary phenylacetylglutamine. Assuming the 13C enrichment of breath CO2 was that of the CO2 fixed by pyruvate, the enrichment to be expected in blood glucose, if all hepatic glucose production had been by gluconeogenesis, was then estimated. That estimate was compared with the actual enrichment in blood glucose, yielding the fraction of glucose production due to gluconeogenesis. Relative rates were similar in the 60-h fasted healthy subjects and the diabetic patients. Conversion of oxaloacetate to phosphoenolpyruvate was two to eight times Krebs cycle flux and decarboxylation of pyruvate to acetyl-CoA, oxidized in the cycle, was less than one-30th the fixation by pyruvate of CO2. Thus, in estimating the contribution of a gluconeogenic substrate to glucose production by measuring the incorporation of label from the labelled substrate into glucose, dilution of label at the level of oxaloacetate is relatively small. Pyruvate cycling was as much as one-half the rate of conversion of pyruvate to oxaloacetate. Glucose and glutamate carbons were derived from oxaloacetate formed by similar pathways if not from a common pool. In the 60-h fasted subjects, over 80% of glucose production was via gluconeogenesis. In the diabetic subjects the percentages averaged about 45%.
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PMID:Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients. 755 86

The factors determining the outcome of human fetal islet transplantation in patients with insulin-dependent diabetes mellitus (IDDM) remain unclarified. In this study we analysed the ratio between immunoregulatory lymphocyte subpopulations in order to search for a possible marker of the immune destruction of transplanted islets. Human fetal islets were isolated by collagenase digestion, cultured for 14 days at 37 degrees C, 5% CO2, and implanted under fascia of m. rectus abdominis in 7 IDDM patients (5 pancreata per patient). After transplantation we evaluated simultaneously the level of metabolic control through HbA1c values determined by chromatography, the capacity of insulin secretion through the C-peptide levels (determined by radioimmunoassay) before and 6 minutes after 1 mg glucagon i.v. stimulation, and the ratio between CD4+ and CD8+ lymphocytes determined by immunofluorescence using monoclonal antibodies. We found that metabolic control after transplantation was improved together with the decrease of the insulin daily dose, and the improvement was simultaneous to the increase of both basal and glucagon-stimulated C-peptide levels. Four months after transplantation we detected a remarkable decrease in the secretion capacity, accompanied by the necessity for an increase in daily insulin dose to maintain optimal metabolic control. However, the loss of islet function was preceded by the increase in CD4+/CD8+ ratio, thus reflecting the presumable accumulation of CD4+ inducer T-lymphocytes. When the islet secretion capacity was destroyed, we found a decrease in CD4+/CD8+ ratio, reflecting the recruitment of CD8+ effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Human fetal pancreatic islet transplantation in insulin-dependent diabetics: possibilities of early detection of transplant destruction]. 759 Apr 18

Microvascular clearance of FITC-Dextran 150 (fluorescein isothiocyanate dextran, MW 150,000) was studied in cremaster muscles of control (BB/W-R) and diabetic (BB/W-DM) rats following daily injections of a full (FD) or a 1/2 (reduced; RD) dose of insulin. The cremaster muscle was placed in an intravital chamber and superfused with bicarbonate buffer (pH 7.4, equilibrated with 95% N2-5% CO2). A 1-hour period of stabilization was followed by the i.v. injection of FITC-dextran 150 and an equilibration period of 45 min. Suffusate samples were collected for 1 h for control measurements. Following this period, bradykinin was applied topically at a concentration of 10(-7) M. Samples were collected for a final hour for the assessment of clearance. The mean +/- SEM FITC-dextran 150 clearance values (microliter/60 min/g) for BB/W-R, BB/W-DM FD, and BB/W-DM RD were 11.5 +/- 1.8, 14.8 +/- 3.4, and 90.5 +/- 12.0, respectively. The corresponding values after topical application of 10(-7) M bradykinin were 23.7 +/- 5.9, 24.2 +/- 4.4, and 98.7 +/- 25.0. Our results indicate that bradykinin evokes a twofold increase in FITC-dextran 150 clearance in the BB/W-R (control) animals and in the BB/W-DM rats receiving full-dose insulin. In contrast, bradykinin does not further enhance the eightfold increase in FITC-Dextran 150 clearance observed in the reduced-insulin dose-treated BB/W-DM group. Thus, our data show that insulin, administered at a full dose, protects the functional integrity of microvascular perm-selectivity in diabetes mellitus.
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PMID:Microvascular clearance of macromolecules in skeletal muscle of spontaneously diabetic rats. 768 75

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.
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PMID:Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis. 776 51

Insulin secretion and glucose metabolism were compared in islets isolated from GK Wistar rats (a non-obese, spontaneous model of non-insulin-dependent diabetes mellitus) and control Wistars aged 8 and 14 weeks. By 8 weeks of age, GK Wistar rats were clearly diabetic as indicated by non-fasting plasma glucose concentrations and impaired glucose tolerance. Islet insulin content was not significantly different to controls at either age. In islets from 14-week-old GK Wistar rats glucose-stimulated insulin release (6-16 mmol/l glucose) was significantly reduced to 25-50% of controls in static incubations (p < 0.001). In perifusion, glucose-stimulated insulin release was reduced by 90% for first phase (p < 0.01) and by 75% for second phase (p < 0.05). The responses to arginine and 2 alpha Ketoisocaproate in islets were similar to those in controls. In contrast, islets isolated from 8-week-old GK Wistar rats exhibited no significant reduction in glucose-stimulated insulin secretion in static incubations. In perifusion, although both first and second phases of glucose-stimulated insulin release were slightly reduced, these were not significantly different to controls. Islets from 8-week-old GK Wistar rats failed however to respond to stimulation by glyceraldehyde. Raising the medium glucose concentration to 16 mmol/l significantly increased rates of glucose utilisation ([3H] H2O production from 5-[3H] glucose) and oxidation ([14C] CO2 production from U-[14C] glucose) in islets isolated from 8-week-old control and GK Wistar rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of islet secretory function in the development of diabetes in the GK Wistar rat. 780 15

Increased energy substrate metabolism accompanies the functional activation of extrathymic immunocytes in the autoimmune BB diabetic rat, but the specific cells responsible have not been identified. To determine the possible contribution of lymphocytes to the elevated metabolism of glucose and glutamine, mesenteric lymph node cells were selected because they contain few macrophages or natural killer (NK) cells. Results from diabetic (BBd, n = 7) and non-diabetes-prone (BBn, n = 7) rats were compared with those from streptozotocin-induced diabetic (STZ-BBn, n = 6) rats. In BBd cells, all measured metabolites of glutamine (CO2, glutamate, aspartate, and NH3) in the presence of 5 mM glucose were elevated (1.5- to 2.5-fold) compared with BBn. In contrast, the only product of glucose metabolism (in the presence of 2 mM glutamine) that was increased was pyruvate (1.6-fold). All measured products of glucose metabolism were significantly lower in cells from STZ-BBn than from BBn rats. Products from glutamine did not differ. Calculated potential ATP production was greater (p < 0.05) in BBd than in BBn and STZ-BBn cells (86 +/- 5 vs. 65 +/- 2 and 53 +/- 5 nmol.2 h-1 x 10(-6) cells, respectively). However, in BBn and STZ-BBn rats, about three quarters of the cells were T (CD5+) cells and one quarter were B (MARK-1+) cells, whereas in BBd three quarters of the cells were MARK-1+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced metabolism of glucose and glutamine in mesenteric lymph node lymphocytes from spontaneously diabetic BB rats. 782 92

A marked decrease in the activity of the amiloride-sensitive Na+/H+ exchanger has been demonstrated in hearts from streptozotocin (STZ)-induced diabetic rats. The aim of this study was to investigate the contribution of other specific sarcolemmal transport mechanisms to intracellular pH (pHi) recovery upon reperfusion in STZ-induced diabetic rat hearts and their relation to recovery of ventricular function. Isovolumic rat hearts were submitted to a zero-flow ischemic period of 28 min at 37 degrees C and then reperfused for 28 min. The time course of pHi decline during ischemia and of recovery on reperfusion was followed by means of 31P-labeled NMR. The perfusion buffers used were either HEPES or CO2/HCO3-. An HCO3(-)-dependent (amiloride-insensitive) mechanism contributed to pHi recovery after ischemia in the diabetic rat hearts. Even when the Na+/H+ exchanger was blocked by amiloride in nominally HCO3(-)-free solution, a rapid rise in pHi occurred during the first 3 min of reperfusion. The early rise in pHi was reduced by external lactate and inhibited by alpha-cyano-4-hydroxycinnamate. This suggested that a coupled H(+)-lactate efflux may be a major mechanism for acid extrusion in the initial stage of reperfusion. The observation of a higher functional recovery on reperfusion in diabetic hearts is in accordance with previous studies using HCO3- buffer. However, this study shows that a good recovery of function occurred even more rapidly in diabetic hearts receiving HEPES-buffered solution than in those receiving HCO3(-)-buffered solution. This suggests that the HCO3(-)-dependent mechanism of regulation may be depressed in diabetic rat hearts.
Diabetes 1995 Feb
PMID:Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts. 785 41

To study the cellular mechanisms underlying fructose-induced insulin resistance in rats, the effects of fructose feeding on insulin-stimulated glucose transport, oxidation and incorporation into lipids in epididymal adipocytes were evaluated in 27 normal and 27 noninsulin-dependent diabetic male Sprague-Dawley rats. Diabetes was induced by streptozotocin injection 2 d after birth. At 5 wk of age, both normal and diabetic rats were fed a diet containing 62% carbohydrate as fructose, dextrose or cornstarch. Fructose feeding for 6 wk induced glucose intolerance in normal rats (P < 0.05) and aggravated that of diabetic rats (P < 0.05). Plasma triacylglycerol concentration was higher in fructose-fed than in starch-fed or dextrose-fed rats (P < 0.05). Adipocytes of fructose-fed rats had significantly lower maximum insulin-stimulated glucose incorporation into total lipids than those of rats fed starch, and tended (P = 0.22) to have lower production of CO2 from glucose than adipocytes of the other dietary groups. Glucose transport in adipocytes of dextrose-, starch- and fructose-fed rats did not differ. We conclude that in both normal and diabetic rats, a chronic fructose-rich diet induced hypertriacylglycerolemia, glucose intolerance and insulin resistance of adipocytes.
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PMID:A fructose-rich diet decreases insulin-stimulated glucose incorporation into lipids but not glucose transport in adipocytes of normal and diabetic rats. 786 Dec 42

The purposes of this study were (i) to determine if ventilatory control is altered in streptozotocin (STZ)-induced diabetic rats and (ii) to determine whether insulin treatment of diabetic rats could prevent ventilatory abnormalities. Male Sprague-Dawley rats were randomly assigned to three groups: control (n = 10), diabetic (n = 9), and diabetic treated with insulin (n = 9). The diabetic group exhibited a progressive reduction of tidal volume, minute ventilation, and CO2 production compared with the control and diabetic treated with insulin groups over the 4 week period. Furthermore, the ventilatory responses to the hypercapnic (3%, 6%, 9% CO2) and hypoxic (10% O2) gas challenges were significantly less in the diabetic rats than those of the control and diabetic and insulin treated groups by the third and fourth week. Ventilation and ventilatory responses to hypercapnia and hypoxia were similar in the control group and the diabetic treated with insulin group at the end of the study. In conclusion, uncontrolled diabetes induced in rats by STZ treatment resulted in altered control of ventilation that could be prevented by insulin therapy.
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PMID:Altered control of ventilation in streptozotocin-induced diabetic rats. 793 52


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