HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Amin, R. H. Articles by Leff, T. PubMed PubMed Citation Articles by Amin, R. H. Articles by Leff, T.

RESEARCH ARTICLE

Selective Activation of PPAR in Skeletal Muscle

Induces Endogenous Production of Adiponectin and Protects Mice From Diet-Induced Insulin Resistance

¹Wayne State Univesity ²Auburn University ³Abbott Laboratories ⁴Eli Lilly Co. ⁵Wayne State University School of Medicine

Submitted 17 July 2009 ; revised 22 September 2009 ; accepted in final form 18 October 2009

The nuclear receptor PPAR plays key role in regulating whole-body glucose homeostasis and insulin sensitivity. Although it is expressed most highly in adipose, it is also present at lower levels in many tissues including skeletal muscle. The role muscle PPAR plays in metabolic regulation and in mediating the antidiabetic effects of the thiazolidinediones is not understood. The goal of this work was to examine the molecular and physiological effects of PPAR activation in muscle cells. We found that pharmacological activation of PPAR in primary cultured myocytes, and genetic activation of muscle PPAR in muscle tissue of transgenic mice, induced the production of adiponectin directly from muscle cells. This muscle-produced adiponectin was functional and capable of stimulating adiponectin signaling in myocytes. In addition, elevated skeletal muscle PPAR activity in transgenic mice provided a significant protection from high fat diet-induced insulin resistance and associated changes in muscle phenotype, including reduced myocyte lipid content and an increase in the proportion of oxidative muscle fiber types. Our findings demonstrate that PPAR activation in skeletal muscle can have a significant protective effect on whole body glucose homeostasis and insulin resistance, and that myocytes can produce and secrete functional adiponectin in a PPAR dependent manner. We propose that activation of PPAR in myocytes induces a local production of adiponectin that acts on muscle tissue to improve insulin sensitivity.

Diabetes; PPARg; adiponectin; gene expression; thiazolidinediones