File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Nephrin is critical for the action of insulin on human glomerular podocytes

TitleNephrin is critical for the action of insulin on human glomerular podocytes
Authors
Issue Date2007
Citation
Diabetes, 2007, v. 56 n. 4, p. 1127-1135 How to Cite?
AbstractThe leading causes of albuminuria and end-stage renal failure are secondary to abnormalities in the production or cellular action of insulin, including diabetes and hyperinsulinemic metabolic syndrome. The human glomerular podocyte is a critical cell for maintaining the filtration barrier of the kidney and preventing albuminuria. We have recently shown this cell to be insulin sensitive with respect to glucose uptake, with kinetics similar to muscle cells. We now show that the podocyte protein nephrin is essential for this process. Conditionally immortalized podocytes from two different patients with nephrin mutations (natural human nephrin mutant models) were unresponsive to insulin. Knocking nephrin down with siRNA in wild-type podocytes abrogated the insulin response, and stable nephrin transfection of nephrin-deficient podocytes rescued their insulin response. Mechanistically, we show that nephrin allows the GLUT1- and GLUT4-rich vesicles to fuse with the membrane of this cell. Furthermore, we show that the COOH of nephrin interacts with the vesicular SNARE protein VAMP2 in vitro and ex vivo (using yeast-2 hybrid and coimmunoprecipitation studies). This work demonstrates a previously unsuspected role of nephrin in vesicular docking and insulin responsiveness of podocytes. © 2007 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/195446
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCoward, RJM-
dc.contributor.authorWelsh, GI-
dc.contributor.authorKoziell, A-
dc.contributor.authorHussain, S-
dc.contributor.authorLennon, R-
dc.contributor.authorNi, L-
dc.contributor.authorTavaré, JM-
dc.contributor.authorMathieson, PW-
dc.contributor.authorSaleem, MA-
dc.date.accessioned2014-02-28T06:12:10Z-
dc.date.available2014-02-28T06:12:10Z-
dc.date.issued2007-
dc.identifier.citationDiabetes, 2007, v. 56 n. 4, p. 1127-1135-
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/195446-
dc.description.abstractThe leading causes of albuminuria and end-stage renal failure are secondary to abnormalities in the production or cellular action of insulin, including diabetes and hyperinsulinemic metabolic syndrome. The human glomerular podocyte is a critical cell for maintaining the filtration barrier of the kidney and preventing albuminuria. We have recently shown this cell to be insulin sensitive with respect to glucose uptake, with kinetics similar to muscle cells. We now show that the podocyte protein nephrin is essential for this process. Conditionally immortalized podocytes from two different patients with nephrin mutations (natural human nephrin mutant models) were unresponsive to insulin. Knocking nephrin down with siRNA in wild-type podocytes abrogated the insulin response, and stable nephrin transfection of nephrin-deficient podocytes rescued their insulin response. Mechanistically, we show that nephrin allows the GLUT1- and GLUT4-rich vesicles to fuse with the membrane of this cell. Furthermore, we show that the COOH of nephrin interacts with the vesicular SNARE protein VAMP2 in vitro and ex vivo (using yeast-2 hybrid and coimmunoprecipitation studies). This work demonstrates a previously unsuspected role of nephrin in vesicular docking and insulin responsiveness of podocytes. © 2007 by the American Diabetes Association.-
dc.languageeng-
dc.relation.ispartofDiabetes-
dc.titleNephrin is critical for the action of insulin on human glomerular podocytes-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.2337/db06-0693-
dc.identifier.pmid17395751-
dc.identifier.scopuseid_2-s2.0-34047099749-
dc.identifier.volume56-
dc.identifier.issue4-
dc.identifier.spage1127-
dc.identifier.epage1135-
dc.identifier.isiWOS:000245697200027-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats