Abstract 13412: Differential Insulin-dependent Signaling Pathways Modulated by Hydrogen Peroxide in Cardiac Myocytes

Hydrogen peroxide (H2O2) has long been implicated in insulin signal transduction, yet the mechanisms whereby insulin regulates intracellular H2O2 to modulate physiological responses remain obscure. Here we explore the roles of H2O2 in regulation of insulin pathways in cardiac myocytes. We found that insulin inhibits cardiac myocyte beta adrenergic physiological and biochemical responses. We found that catalase (which degrades H2O2) completely blocks the ability of insulin to activate the insulin-responsive kinases Akt/mTOR and also to attenuate beta adrenergic receptor-mediated increases in myocyte contractility. These insulin responses are abrogated in a mouse model of type 2 diabetes, establishing a key role for H2O2-dependent pathways in the diabetic heart. To directly probe intracellular H2O2 responses to insulin in cardiac myocytes, we constructed a novel recombinant AAV9 vector expressing the fluorescent H2O2 biosensor HyPer, which we used to infect mice in vivo. We isolated cardiac myocytes from mi...