| Insulin signaling to the glomerular podocyte is critical for normal kidney function. | |
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MedLine Citation:
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PMID: 20889126 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell metabolism Volume: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 329-40 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Academic Renal Unit, School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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G0501901//Medical Research Council; //Wellcome Trust |
| Comments/Corrections | |
Comment In:
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Cell Metab. 2010 Oct 6;12(4):311-2
[PMID:
20889121
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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