Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria.

PURPOSE OF REVIEW: In diabetic nephropathy, insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of diabetic nephropathy will be discussed. RECENT
FINDINGS: Whereas normal podocytes take up glucose in response to insulin, diabetic podocytes become insulin resistant in experimental diabetic nephropathy prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independent of their systemic effects on the metabolic control of diabetes.
SUMMARY: We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of diabetic nephropathy in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of diabetic nephropathy. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of diabetic nephropathy. Understanding the role of podocytes in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of diabetic nephropathy, it may affect current strategies for prevention and treatment of diabetic nephropathy, and it may allow the identification of novel therapeutic targets.