Effects of troglitazone and insulin on glucose production in cultured hepatocytes isolated from rats on high fat diet.

Increased dietary fat intake in general, and saturated fat specifically, will lead to the impairment of insulin action. The aim of this study was to find out the changes in hepatic glucose output in dependence of fat diet and a possible direct action of insulin and trogitazone in hepatocytes. Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h in M 199 serum-free medium. The glucose production in hepatocytes isolated from rats on high fat diet (unsaturated fat) was 79% higher compared to control and even 139% higher than in rats on high-fat diet (saturated fat). Troglitazone significantly decreased the glucose production in hepatocytes obtained from rats on unsaturated fat diet. The troglitazone in presence of insulin totally normalized glucose production but also only in hepatocytes obtained from rats on unsaturated-fat diet. The troglitazone showed an insulinomimetic as well as insulin-sensitizing effect but only in rats on unsaturated-fat diet.