Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic nephropathy (DN) in patients with type 1 and type 2 diabetes. Although the mechanisms underlying the development of podocyte loss are not completely understood, hyperglycemia has been proposed as one of the most important causal factors. The importance of insulin actions in podocyte survival and function has recently generated much interest. The aims of this project are to characterize the changes in insulin expression and actions in cultured podocytes exposed to high glucose levels and to investigate the mechanisms of insulin resistance in diabetic animal models of type 1 and 2 diabetes.