Insulin signaling to the glomerular podocyte is critical for normal kidney function

Gavin I Welsh, Lorna J Hale, Vera Eremina, Marie Jeansson, Yoshiro Maezawa, Rachel Lennon, Deborah A Pons, Rachel J Owen, Simon C Satchell, Mervyn J Miles, Christopher J Caunt, Craig A McArdle, Hermann Pavenstädt, Jeremy M Tavaré, Andrew M Herzenberg, C Ronald Kahn, Peter W Mathieson, Susan E Quaggin, Moin A Saleem, Richard J M Coward

Research output: Contribution to journalArticle (Academic Journal)

266 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)329 - 340
Number of pages12
JournalCell Metabolism
Volume12
Issue number4
DOIs
Publication statusPublished - 6 Oct 2010

Bibliographical note

Copyright © 2010 Elsevier Inc. All rights reserved.

Keywords

  • Animals
  • Diabetic Nephropathies
  • Insulin
  • Kidney
  • Kidney Glomerulus
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Podocytes
  • Receptor, Insulin
  • Signal Transduction

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