Developing Inhibitors of the STARS/SRF Pathway for Treatment of Type 2 Diabetes

DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) has reached epidemic proportions in the United States, affecting an estimated 8.3% of the population. Unfortunately, the majority of individuals with diabetes continue to have suboptimal control ofglucose, therefore new and improved approaches to prevention and treatment are sorely needed. Dr. Mary Elizabeth Patti's laboratory at the Joslin Diabetes Center (JDC) has recently identified a novel pattern of gene expression in skeletal muscle from human patients with established T2D. This pattern includes increased expression of genes regulated by serum response factor (SRF) and its upstream regulatory protein STARS (striated muscle activator of Rho-dependent signaling). Importantly, this pattern is also present in those at risk for disease based on family history, potentially linking this to T2D-risk. Genetic and pharmacologic data from the Patti lab (JDC) robustly indicate that modulation of the STARS-SRF pathway can regulate muscle insulin resist