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Cell Metab. 2010 Oct 6;12(4):329-340. doi: 10.1016/j.cmet.2010.08.015.

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

Author information

1
Academic Renal Unit, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK.
2
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada.
3
School of Physics, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK.
4
Department of Molecular Pharmacology, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK.
5
Department of Internal Medicine D, Nephrology and Hypertension, University Clinics Muenster, Muenster 48149, Germany.
6
School of Biochemistry, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK.
7
Department of Pathology, University Health Network and University of Toronto, Ontario M5G 2C4, Canada.
8
Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA.
9
Academic Renal Unit, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada. Electronic address: richard.coward@bristol.ac.uk.

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.

PMID:
20889126
PMCID:
PMC4949331
DOI:
10.1016/j.cmet.2010.08.015
[Indexed for MEDLINE]
Free PMC Article

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