Effects of Vanadate on Oleic Acid Induced Insulin Resistance in Cultured Rat Hepatocytes

Insulin resistance is a common phenomenon in obesity and type 2 diabetes (1). It has been demonstrated that, among other factors, acutely elevated free fatty acids can induce insulin resistance in both peripheral tissues and liver (2). Free fatty acids also reduce insulin binding and degradation, and exert an important modulating effect on insulin action in isolated rat hepatocytes (3). They can also increase hepatic gluconeogenesis (4). Vanadate caused longterm and marked improvement of glucose homeostasis in obese fa/fa rats and diabetic ob/ob mice (5,6). Vanadate also improved hepatic and peripheral insulin sensitivity in patients with non-insulin dependent diabetes mellitus (7). However, these results are in contrast to the finding that acute infusion of vanadate stimulates glucose production in perfused livers from fed rats (8). Besides these metabolic effects, vanadate-dependent inhibition of phosphatase, increased insulin binding to target cells and enhanced tyrosine phosphorylation of insulin receptor have also been reported, all suggesting the possible modulatory action of vanadate on insulin signaling (9,10). This could be the main way of vanadate action on insulin resistance and glucose homeostasis. The aim of the study was to investigate this hypothesis by studying the effects of vanadate on amino acid transport in cultured rat hepatocytes, which became insulin-resistant after acute oleic acid treatment.