engleski

Vanadate modulate hepatic insulin resistance in cultured hepatocytes isolated from rats on high-fat diets (saturated and unsaturated fat)

Increased hepatic glucose production correlates well with fasting hyperglycemia in obesity and Type 2 diabetes. It is characterized by hormonal imbalance, hyperglucagonemia and insulin resistance. Vanadate treatment improves glucose homeostasis in vivo. High-fat feeding induced insulin resistance. We examined high-fat diets (saturated and unsaturated fat) in relation to hepatic glucose output and direct action of insulin, glucagon and vanadate in cultured rat hepatocytes. Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h. The hepatic glucose production was measured in glucose free medium, by incubating hepatocytes without or with insulin (0, 08 μ M/L), glucagon (0, 2 μ M/L), or with vanadate (1mM/L). Glucose was determined enzimatically, with glucose oxidase. Basal glucose production was significantly 33% (p<0, 01) higher in hepatocytes isolated from a saturated fat-fed animals than in those of unsaturated fat. The glucagon 100 % increased glucose production in hepatocytes from rats on high saturated fat diet (p<0, 01). Glucagon effect was 55 % higher in hepatocytes from rats on high unsaturated fat versus saturated fat-fed animals (p<0, 01). Insulin did not decrease basal or glucagon-stimulated glucose production. Vanadate decreased glucagon-stimulated glucose production in hepatocytes from unsaturated fat-fed rats for 50 %, (p<0, 01). Both high-fat diets caused hepatic insulin resistance. Saturated fat diet induced greater alterations in insulin action, greater severity and extent of hepatic insulin resistance in association with greater increase of basal glucose production and lower sensitivity to glucagon. Vanadate showed an insulinomimetic effect only in hepatocytes isolated from unsaturated fat-fed animals.

hepatocytes; high-fat feeding; insulin; insulin resistance

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