Journal article
Pigment Epithelium-Derived Factor Contributes to Insulin Resistance in Obesity
S Crowe, LE Wu, C Economou, SM Turpin, M Matzaris, KL Hoehn, AL Hevener, DE James, EJ Duh, MJ Watt
Cell Metabolism | CELL PRESS | Published : 2009
Abstract
Obesity is a major risk factor for insulin resistance; however, the factors linking these disorders are not well defined. Herein, we show that the noninhibitory serine protease inhibitor, pigment epithelium-derived factor (PEDF), plays a causal role in insulin resistance. Adipocyte PEDF expression and serum levels are elevated in several rodent models of obesity and reduced upon weight loss and insulin sensitization. Lean mice injected with recombinant PEDF exhibited reduced insulin sensitivity during hyperinsulinemic-euglycemic clamps. Acute PEDF administration activated the proinflammatory serine/threonine kinases c-Jun terminal kinase and extracellular regulated kinase in both muscle and ..
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Awarded by National Institutes of Health
Funding Acknowledgements
We would like to thank Drs. Sebastian Jorgensen, Georg Ramm, Mark Raftery, and Anne Poljak for technical advice and Ui Jeong Yun and Brian Drew for technical assistance. These studies were supported by research grants from the National Health and Medical Research Council (NHMRC) of Australia and the Diabetes Australia Research Trust. S.M.T. is supported by a Dora Lush Scholarship and MJW by an R. Douglas Wright Career Development Award from the NHMRC and a Monash Fellowship. E.J.D. is a recipient of an RPB Career Development Award and is supported by the Juvenile Diabetes Research Foundation. A.L.H. is supported by the National Institutes of Health