Differential effects of blood insulin levels on microsomal enzyme activities from hepatic and extrahepatic tissues of male rats (original) (raw)
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Canadian Journal of Physiology and Pharmacology, 1990
The activity of in vitro glutathione S-transferase towards 1-chloro-2,4-dinitrobenzene was examined in liver, renal cortex, and small intestine (duodenum, jejunum, ileum) after the in vivo treatment of male Wistar rats with streptozotocin or alloxan. The studies were performed at 2, 10, 24, and 48 h and 7 and 15 days after streptozotocin treatment or 24 and 48 h after alloxan treatment. The results indicated that while the blood levels of insulin–glucose did not show variations, there were no alterations of the glutathione S-transferase activity in the tissues tested. On the other hand, when the treatments caused modifications on blood insulin–glucose levels, there were changes of glutathione S-transferase activity in all tissues (except in the ileum) in such a way that a direct relationship between plasma insulin levels and glutathione S-transferase activity could be demonstrated. These results were also confirmed through insulin administration to control and diabetic rats. The dat...
Diabetologia, 1989
In isolated rat pancreatic islets exogenous glutathione which is not able to penetrate into cells, augmented glucose (11.1 mmol/1)-mediated insulin release. In the presence of a non-stimulatory glucose concentration (2.8 mmol/1) glutathione had no effect. The half-maximal synergistic action of glutathione on insulin secretion was observed at approximately 8.0 ktmol/1. This concentration of glutathione is similar to that found in the plasma of non-fasted anaesthetised rats (6.5 lxmol/1). Oral ingestion of glucose increased the arterial plasma glutathione in rats. Our data provide for the first time indirect evidence for a modulating effect of plasma glutathione in postprandial glucose-mediated insulin secretion which appears to be located at the extracellular site of islet cells.
Insulin resistance in uremia: in vitro model in the rat liver using human serum to study mechanisms
Metabolism, 1986
We have previously demonstrated in a rat model of chronic uremia that the liver is resistant to insulin. To further investigate the mechanism(s) of insulin resistance in uremia, primary cultures of normal rat hepatocytes were incubated with varying dilutions (1 /lO to 1 /lO,OOO) of sera from undialyzed end stage uremic and normal humans for 20 hours. We then studied insulin action, binding, and postbinding events. Dilutions of uremic sera as low as 1 /l,OOO rendered the hepatocytes resistant to maximal concentrations of insulin with regard to [%]acetate incorporation into lipids. The dose response curve for insulin-stimulated
Changes in hepatic glutathione metabolism in diabetes
Diabetes, 1991
Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes. In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted. Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone. In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic 7-glutamyltransferase activity was considerably increased. These changes were not reproduced by food deprivation. The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic 7-glutamyl cycle. We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction. Diabetes 40:344-48, 1991 T he tripeptide glutathione is present in all cell types and is important in the regulation of the redox state and the protection of cells from oxidative damage (1,2). Its importance is exemplified by the findings that fibroblasts and hepatocytes depleted of glutathione die prematurely, a phenomenon prevented by the presence of an antioxidant (3,4).
The Journal of Membrane Biology, 2013
This study investigated the possible role of glutathione (GSH) in diabetic complications and its biochemical safety in experimental diabetic rats. Serum biochemical parameters and the histology of the pancreas were investigated. Seven rats were separated as controls. To create the diabetes in rats, 45 mg/kg single-dose streptozotocin (STZ) was administered i.p. The treatment was continued for 1 month. STZ was administered to the diabetes ? GSH group, then reduced GSH, dissolved in isotonic salt solution (200 mg/kg), was applied i.p. two times a week. The GSH group received i.p. GSH. Serum biochemical parameters were determined by autoanalyzer. Immunohistochemical procedures were used to determine the percentage of the insulin-immunoreactive b-cell area in the islets of Langerhans. The biochemical parameters changed to different degrees or did not change. Pancreatic cells of the control and GSH groups were healthy, but in the diabetic and GSH-treated diabetic groups we found damage in different numbers. The results from these analyses show that GSH supplementation can exert beneficial effects on pancreatic cells in STZ-induced diabetic rats and can safely be used for therapy in and protection from diabetes and complications of diabetes.
Effect of diabetes on enzymes involved in rat hepatic corticosterone production
2010
Background: Numerous studies have explored the etiologic or permissive role of 11b-hydroxysteroid dehydrogenase (11b-HSD1) in obesity and Type 2 diabetes, biochemical conditions often with concurrent hyperinsulinism. In contrast, there are limited data on the effect of insulin deficiency (i.e. Type 1 diabetes) on 11b-HSD1 or endoplasmic reticulum enzymes that generate the reduced pyridine cofactor NADPH. Thus, the aim of the present study was to examine the effect of insulin-deficient, streptozotozin diabetes on key microsomal enzymes involved in rat hepatic corticosterone production. Methods: After rats had been rendered diabetic with streptozotocin and some had been treated with insulin (2-6 units, s.c., long-acting insulin once daily) for 7 days, hepatic microsomes were isolated. Serum corticosterone and fructosamine were obtained premortem. Intact microsomes were incubated in vitro and 11b-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), and isocitrate dehydrogenase (IDH) measured. Results: Although diabetes markedly altered body weight gain and serum protein glycosylation (assessed by fructosamine), there was no significant change in hepatic 11b-HSD1 reductase activity, with or without insulin treatment. However, serum corticosterone levels were significantly correlated with 11b-HSD1 reductase activity when all groups were analyzed together (P < 0.05). Untreated diabetes modified (P < 0.01) two hepatic microsomal NADPH-generating enzymes, namely H6PDH and IDH, resulting in a 37% decrease and 14% increase in enzyme levels, respectively. Conclusions: Consistent with most in vivo studies, chronic insulin deficiency with attendant hyperglycemia does not significantly modify hepatic 11b-HSD1 reductase activity, but does alter the activity of two microsomal enzymes coupled with pyridine cofactors.
Chemosphere, 1999
Antioxidant enzymes in liver and small intestine were investigated using control and streptozotocin diabetic rats fed diets with 5% olive, sunflower or fish oil for five weeks. In liver, Glutathione Peroxidase and Superoxide Dismutase decreased and in intestine Glutathione-S-transferase (GST) increased by diabetes. In isolated jejunum and ileum, this increase in GST activity was due to an increase in GST-a and -~t isoenzymes in jejunum and GST-~, la and -re in ileum. Since GST plays an important role in protecting tissues from oxidative damage, our results highlight the role of the intestine against free radicals in physiological or pathological situations.
Whole body and hepatic insulin action in normal, starved, and diabetic rats
1991
In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo doseresponse relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-"HIglucose infusion. Twelve-hour fasting (basal) HGP was 3.0 t 0.2, 2.1 t 0.2, and 5.4 t 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from t20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 t 11 pU/ml) in S and unchanged (113 t 21 pU/ml) in D compared with N rats (105 t 10 pU/ml). Insulin responsiveness was unchanged (12.4 t 0.8 mg/min) in S and decreased (8.5 t 0.8 mg/min) in D compared with N rats (12.3 t 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 t 10 pU/ml) in S and decreased (157 t 21 pU/ml) in D compared with N rats (71 t 5 ,uU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (lo-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se. MATERIALS AND METHODS Animals and housing. Male Wistar rats (300-350 g) with free access to a complete laboratory rat diet
Life Sciences, 2006
Low-dose acetylsalicylic acid (ASA) treatment is a standard therapeutic approach in diabetes mellitus for prevention of long-term vascular complications. The aim of the present work was to investigate the effect of long-term ASA administration in experimental diabetes on activities of some liver enzymes: glutathione peroxidase (GSHPx), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). Blood glucose, glycated hemoglobin, as well as plasma ALT and AST activities increased in rats with streptozotocin-induced experimental diabetes. The long-term hyperglycemia resulted in decreased activities of GSHPx (by 26%), catalase (by 34%), GST (by 38%) and G6PDH (by 27%) in diabetic animals. We did not observe increased accumulation of membrane lipid peroxidation products or altered levels of reduced glutathione in livers. The linear correlation between blood glucose and glycated hemoglobin in diabetic animals was distorted upon ASA treatment, which was likely due to a chemical competition between nonenzymatic protein glycosylation and protein acetylation. The long-term ASA administration partially reversed the decrease in GSHPx activity, but did not influence the activities of catalase and GST in diabetic rats. Otherwise, some decrease in these parameters was noted in ASA-treated nondiabetic animals. Increased ASA-induced G6PDH activity was recorded in both diabetic and nondiabetic rats. While both glycation due to diabetic hyperglycemia and ASA-mediated acetylation had very similar effects on the activities of all studied enzymes but G6PDH, we conclude that non-enzymatic modification by either glucose or ASA may be a common mechanism of the observed convergence.