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Effects of troglitazone and vanadate on insulin resistance in cultured hepatocytes isolated from rats on high fat diet

Insulin resistance is a common phenomenon in obesity and Type 2 diabetes. Increased dietary fat intake in general, and saturated fat specifically, will lead to impairment of insulin action. The aim of this study was to find out changing of hepatic glucose output in dependence of fat diet and possible direct action of insulin and possible role of PKC and receptor tyrosine-kinase activity in insulin signal pathway and insulin. Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h in M 199 serum-free medium. The glucose production was measured by incubating the cultures in glucose-free Hanks-Hepes medium with addition 10 mmol/l pyruvate. The glucose released into the medium was determined enzymatically with glucose oxidase. The glucose production in hepatocytes isolated from rats on high fat (sunflower oil) diet was 79% higher comparable with standard control and even 139% higher from rats on high saturated fat diet. Insulin did not decrease to a greater extent glucose production in hepatocytes in both experimental groups. Troglitazone significantly decreased glucose production in hepatocytes obtained in rats on sunflower oil diet. Vanadate alone as well as troglitazone in presence of insulin totally normalized glucose production but again only in hepatocytes obtained from rats on sunflower oil diet. Rats on high saturated fat diet had greater severity and extent of insulin resistance, greater increase of hepatic glucose production. Activation of receptor tyrosine-kinase can overcome insulin resistance.

cultured hepatocytes; glucose production; high fat diet; insulin; insulin resistance; protein kinase C; Troglitazone; Vanadate

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