MECHANISM OF INSULIN SENSITIZING EFFECT OF PIOGLITAZONE-ROLE OF ADIPONECTIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: To study the role of adiponectin and its receptors in the insulin sensitizing effect of pioglitazone. RESEARCH PLAN: This is an open label study to evaluate the mechanism of action of pioglitazone on glucose, free fatty acid/lipid metabolism, and adipocytokines, particularly adiponectin levels and its gene expression in skeletal muscle and adipose tissue subjects with type 2 diabetes, impaired glucose tolerance, obese non diabetic subjects and lean healthy controls. Fifteen subjects in each group will receive Pioglitazone 45mg for 16 weeks and will participate in four different studies before and after pioglitazone treatment. METHODS: Each subject will participate in 1) oral glucose tolerance test, 2) hyperinsulinemic euglycemic clamp combined with tracer studies for hepatic glucose production and calorimetry and skeletal muscle biopsy, 3) adipose tissue biopsy, and 4) MRI studies for measurement of intramyocellular and extramyocellular fat. CLINICAL RELEVANCE: This study will help understand the role of adiponectin and its receptors in the insulin sensitizing effect of Pioglitazone and whether this drug has similar beneficial effects in subjects who are at risk of developing diabetes.