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IRS1-Independent Defects Define Major Nodes of Insulin Resistance


Insulin resistance is a common disorder caused by a wide variety of physiological insults, some of which include poor diet, inflammation, anti-inflammatory steroids, hyperinsulinemia, and dyslipidemia. The common link between these diverse insults and insulin resistance is widely considered to involve impaired insulin signaling, particularly at the level of the insulin receptor substrate (IRS). To test this model, we utilized a heterologous system involving the platelet-derived growth factor (PDGF) pathway that recapitulates many aspects of insulin action independently of IRS. We comprehensively analyzed six models of insulin resistance in three experimental systems and consistently observed defects in both insulin and PDGF action despite a range of insult-specific defects within the IRS-Akt nexus. These findings indicate that while insulin resistance is associated with multiple deficiencies, the most deleterious defects and the origin of insulin resistance occur independently of IRS.

Type Journal
ISBN 1550-4131 (Print)
Authors Hoehn, K. L.;Hohnen-Behrens, C.;Cederberg, A.;Wu, L. E.;Turner, N.;Yuasa, T.;Ebina, Y.;James, D. E. :
Publisher Name Cell Metabolism
Published Date 2008-01-01
Published Volume 7
Published Issue 5
Published Pages 421-33
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version