Cell Metabolism
Volume 12, Issue 4, 6 October 2010, Pages 329-340
Journal home page for Cell Metabolism

Article
Insulin Signaling to the Glomerular Podocyte Is Critical for Normal Kidney Function

https://doi.org/10.1016/j.cmet.2010.08.015Get rights and content
Under an Elsevier user license
open archive

Summary

Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycemic “microvascular” complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to insulin. To determine whether insulin signaling in podocytes affects glomerular function in vivo, we generated mice with specific deletion of the insulin receptor from their podocytes. These animals develop significant albuminuria together with histological features that recapitulate DN, but in a normoglycemic environment. Examination of “normal” insulin-responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3K pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. Collectively, this work reveals the critical importance of podocyte insulin sensitivity for kidney function.

Highlights

► Podocyte-specific insulin resistance results in features of diabetic nephropathy ► Insulin signals to the podocyte via the insulin receptor and PI3K/MAPK pathways ► Insulin can rapidly remodel the actin cytoskeleton of the podocyte

Cited by (0)