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

The contribution of hormone-stimulated glycogenolysis to hepatic glucose production was studied in hepatocytes from streptozotocin diabetic rats. To this end, the activation of glycogen phosphorylase by glucagon, vasopressin, and the alpha 1-adrenergic agonist phenylephrine was compared in hepatocytes from normal and diabetic rats and related to glycogen content, glucose production, and microsomal glucose-6-phosphatase activity. Streptozotocin-induced diabetes reduced the glycogen content and the amount of total (a + b) phosphorylase in hepatocytes proportionally to the severity of the disease. In cells from severely diabetic rats (group 1), the responsiveness of activation of phosphorylase to the hormones was reduced by about half, consistent with a 45% reduction in total phosphorylase. In addition, the sensitivity of phosphorylase activation to all hormones investigated was decreased by about 1 order of magnitude or more in cells of this group. In hepatocytes from rats with milder diabetes (group 2), maximal phosphorylase activation reached an intermediate value between that of the control group and of group 1. In response to all hormones investigated, group 2 diabetic rat hepatocytes produced less glucose than control rat liver cells, while in group 1 there was no increase in glucose production at all, presumably because glycogen concentration was too low. However, in group 2 diabetic rat hepatocytes, glucagon-stimulated glucose production, unlike phosphorylase activation, did not show decrease sensitivity, presumably because glucose-6-phosphatase activity is increased by diabetes. Our results thus indicate that hormone-stimulated liver glycogenolysis is unlikely to contribute to enhanced glucose production in insulin-deficient diabetes, despite increased glucose-6-phosphatase activity.
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PMID:Hormone-stimulated glucose production from glycogen in hepatocytes from streptozotocin diabetic rats. 165 43

The effect of glibenclamide treatment on insulin action in isolated fat cells was studied in eight moderately obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of insulin on glucose transport and lipogenesis were determined before and after 3 months of glibenclamide therapy. At the end of the treatment period, mean daytime plasma glucose concentrations were reduced (10.8 +/- 0.4 versus 7.0 +/- 0.3 mmol/L, p less than 0.001) whereas mean daytime plasma insulin level was increased (40 +/- 12 versus 71 +/- 9 mU/L, p less than 0.001). Adipocyte insulin receptor binding as well as basal glucose transport and metabolism were unaffected by drug treatment. In contrast, insulin-stimulated glucose transport and lipogenesis were both significantly enhanced (p less than 0.05). These findings are comparable to those of another study involving seven moderately obese subjects with NIDDM who had biopsies of the lateral vastus muscle taken for measurement of insulin receptor function and glycogen synthase activity before and during 2 months of gliclazide treatment. In that study insulin receptors purified with wheatgerm agglutinin showed unchanged insulin binding and receptor kinase activity. Moreover, gliclazide had no impact on maximal glycogen synthase activity. However, under physiologic hyperinsulinemic conditions gliclazide therapy was associated with an increased sensitivity of glycogen synthase for its allosteric activation by glucose-6-phosphatase (p less than 0.04). In conclusion, sulfonylurea treatment of NIDDM enhances insulin-stimulated peripheral glucose utilization in part through a potentiation of insulin action on adipose tissue glucose transport and lipogenesis and skeletal muscle glycogen synthase.
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PMID:Effects of sulfonylureas on adipocyte and skeletal muscle insulin action in patients with non-insulin-dependent diabetes mellitus. 190 82

Substrate cycles (SC) are formed by a 'forward pathway' (FP) and a 'backward pathway' (BP), the difference between FP and BP forming the 'metabolic flux' (MF) through the route of which the cycle is part. SC modulate regulatory effects, i.e. amplify or reduce the % change in MF compared to the % change in FP and BP, thus affecting the sensitivity to regulatory factors, including hormones. A formula is given to calculate (with an approximation of +/- 0.5) the 'flux response index' (FRI), i.e. the factor by which the % change in FP plus the % change in BP must be multiplied to obtain the % change in metabolic flux, when FP and BP undergo opposite, non-unidirectional changes (as is often the case in metabolic regulation). The formula is: FRI = [( FP + BP)/(FP-BP)]/2. By this formula we evaluated the hepatic activities of glucose-6-phosphatase and glucokinase (which roughly reflect hepatic glucose production and uptake, respectively), i.e. the two enzymes that catalyze the cycle between glucose-6-phosphate (glucose-6-P) and glucose. Based on data obtained in normal, nonobese diabetic and obese diabetic subjects as well as in normal, streptozotocin-diabetic, and obese diabetic (ob/ob) mice, we found that FRI was reduced in non-obese diabetic humans and animals whereas it was increased in obese-diabetic humans and mice, compared to normal controls. Thus, diabetes without obesity decreases, and obesity with diabetes increases, the sensitivity of the glucose-6-P/glucose cycle to regulatory agents.
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PMID:A formula for quantifying the effects of substrate cycles (futile cycles) on metabolic regulation. Its application to glucose futile cycle in liver as studied by glucose-6-phosphatase/glucokinase determinations. 215 82

To obtain insight regarding the mechanism(s) of response of the catalytic unit of glucose-6-phosphatase (D-glucose-6-P phosphohydrolase; EC 3.1.3.9) to glucocorticoid administration and insulin deprivation, the functional enzyme concentration E0 was estimated from presteady-state kinetics by the stopped-flow technique. The E0 values were compared with Vmax values determined by the steady-state kinetic approach. Studies were carried out with detergent-disrupted microsomes from livers of normal fed, 48-h fasted, streptozotocin-diabetic, and triamcinolone-treated rats. All of the treatments caused an increase in E0, but Vmax values were increased only in fasting and diabetes. Km values were unaffected by all the treatments. The increase in Vmax observed with fasted and diabetic rats was explained by an increase in E0 alone. These results showed that insulin deprivation resulted in an increased formation of fully active glucose-6-phosphatase catalytic unit. In contrast, administration of triamcinolone caused an increase in E0 but not in Vmax. It was concluded that glucocorticoid administration may promote formation of catalytic units of glucose-6-phosphatase which are less active than the enzyme normally present or formed in response to insulin deprivation.
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PMID:Hormonal responses of glucose-6-phosphatase catalytic unit studied by stopped-flow analysis. 216 Aug 32

Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3H2O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [3H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals.
Diabetes 1990 Apr
PMID:Glucose cycling in islets from healthy and diabetic rats. 218 Jul 57

Effects of pioglitazone (5-[4-[2-(5-etyl-2-pyridyl)ethoxy] benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) on peripheral and hepatic insulin resistance were examined using genetically obese-hyperglycemic rats, Wistar fatty. Pioglitazone was administered to fatty rats (3 mg/kg/d) and lean rats (10 mg/kg/d) for 6 days. Pioglitazone decreased hyperglycemia and hypertriglyceridemia without affecting hyperinsulinemia in the fatty rats, and significantly reduced plasma levels of triglyceride and insulin without altering normoglycemia in the lean rats. The same rats were subjected to an isotopic method combined with a euglycemic clamp technique for assessing insulin sensitivity in hepatic glucose production (HGP) and peripheral glucose utilization (PGU). HGP decreased and PGU increased in response to infused insulin in the lean rats but did not in the fatty rats, indicating that insulin resistance was present in the liver and peripheral tissues of the fatty rats. Treatment with pioglitazone restored the responses of HGP and PGU to infused insulin in the fatty rats, but did not produce any changes in the lean rats. When the same levels of glycemia and insulinemia were established by 480 mU/h of insulin in both treated and control fatty groups, PGU was 1.5-fold higher and HGP was 3-fold lower in the pioglitazone treated group. Pioglitazone also corrected the abnormality in hepatic enzyme regulation by insulin of the fatty rats: glucose-6-phosphatase decreased and glucokinase increased, suggesting the increased response of the liver to insulin and the resultant suppression of HGP. Therefore, pioglitazone is expected to be useful for treating abnormal glucose and lipid metabolism in non-insulin-dependent diabetes mellitus through reducing insulin resistance of the peripheral tissues and liver.
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PMID:Effects of pioglitazone on hepatic and peripheral insulin resistance in Wistar fatty rats. 219 15

In mice with streptozotocin-induced diabetes of 3 days' duration, the hexokinase/glucose-6-phosphatase (HK/G6Pase) ratio in the kidney was enhanced by 52% (mean +/- SEM: 0.40 +/- 0.04 vs. 0.26 +/- 0.03; p less than 0.02) compared to control mice as a result of a 25% increase of HK (16.68 +/- 0.93 vs. 13.31 +/- 1.04 nmol/min/mg protein; p = 0.05) and a 17% decrease of G6Pase (42.51 +/- 2.75 vs. 51.25 +/- 1.89; p less than 0.05). In contrast, as expected, the corresponding ratio (HK + glucokinase/G6Pase) was strikingly reduced in the liver. In 9-day diabetic mice, the kidney enzyme changes were much smaller; however, in a chronic disease such as diabetes, even minimal deviations from the normal may lead to significant metabolic changes with time. The enhanced HK/G6Pase ratio in the diabetic kidney suggests an increase in glucose utilization. This may contribute to the increased synthesis of glycogen, glycoproteins (including basement membrane) and RNA (via provision of ribose-phosphate) occurring in the diabetic kidney and supports the view that the kidney (as opposed to other tissues) shows an 'anabolic response' to diabetes.
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PMID:Increased hexokinase/glucose-6-phosphatase ratio in the diabetic kidney as index of glucose overutilization. 255 19

Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups. Thus, the potential long-term beneficial effects of feeding diets with a high PUFA/SFA ratio probably have their explanation in metabolic effects distant to their uptake by the intestine.
Diabetes Res 1989 Jan
PMID:Improved intestinal form and function in diabetic rats fed long-term with a polyunsaturated fatty acid diet. 275 39

The aim of this study was to investigate the metabolic effects of short-term fasting in obese diabetic patients and to correlate the observed changes with the activity of hepatic key enzymes in an animal model of obesity-associated diabetes (ob/ob mice, C57BL/6J strain). In obese diabetic patients (ODP), a 72-h fast (causing slight change in body weight) decreased fasting glycemia by 3.82 +/- 0.79 mmoles/l and significantly improved glucose tolerance (OGTT) while reducing basal and stimulated insulinemia, whereas in obese non-diabetic patients (ONDP) only a small decrease in fasting glycemia (1.24 +/- 0.51 mmoles/l) occurred. This suggests that in ODP hyperphagia is a factor contributing to maintain hyperglycaemia and glucose intolerance (in the face of hyperinsulinaemia, indicating insulin resistance). In fed obese hyperglycaemic mice (OHM), which are a good model of the human obesity-associated diabetes, hepatic fructose-1,6-diphosphatase (F16Pase) and glucose-6-phosphatase (G6Pase), involved in glucose production, showed increased activity (+52 and +200 per cent, respectively) compared to control mice (CM), and the ratios of F16Pase and G6Pase to the opposing enzymes phosphofructokinase (PFK1) and glucokinase (GK), i.e. the F16Pase/PFK1 and G6Pase/GK ratios, were increased by 38 and 101 per cent, respectively, suggesting increase in gluconeogenesis and perhaps in glycogenolysis. In the 48-h fasted OHM, F16Pase activity was decreased (-30 per cent) compared to the fed animals, while the activity of G6Pase showed a smaller and statistically not significant change (-22 per cent). In contrast, in the CM a 48-h fasting was associated with a trend toward increased F16Pase (+22 per cent) and G6Pase (+173 per cent). However, since PFK1 and GK decreased to a similar extent in OHM and CM, the F16Pase/PFK1 and G6Pase/GK ratios, basally elevated in the OHM, did not change with fasting, whereas in the CM they showed a striking elevation (+71 and +274 per cent, respectively). The basally elevated F16Pase/PFK1 and G6Pase/GK ratios (functionally linked to glucose production) in the OHM may contribute to maintain hyperglycaemia; in these mice, the lack of further increase in the glucose production-related F16Pase/PFK1 and G6Pase/GK ratios (which occurs in CM) with fasting might allow that the interruption of the afflux of dietary carbohydrates ameliorates the glycaemic level. Similar mechanisms might occur also in the ODP.
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PMID:Metabolic effects of short-term fasting in obese hyperglycaemic humans and mice. 283 Nov 63

The effect of oral administration of vanadate on the transport and hydrolytic components of the glucose-6-phosphatase system in liver homogenates from streptozotocin-induced diabetic rats was examined. Blood glucose was normalized in diabetic rats receiving 0.8 mg/ml vanadate but a catabolic effect was observed on body and liver weight. Significant changes in the coupled reactions for glucose-6-phosphate transport by T1 and hydrolysis by the enzyme were noted. The dramatic elevation in the maximal velocity of glucose-6-phosphatase brought about by diabetes was suppressed by vanadate administration. As a result, the relationship between T1 and the enzyme returned to the normal range. It is concluded that the suppression of glucose-6-phosphate hydrolysis in diabetes may contribute to the normalizing effect of vanadate on blood glucose.
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PMID:Suppression of the hepatic glucose-6-phosphatase system in diabetic rats by vanadate. 285 61


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