HYPERINSULINEMIA INHIBITS MYOCARDIAL PROTEIN-DEGRADATION IN PATIENTS WITH CARDIOVASCULAR-DISEASE AND INSULIN-RESISTANCE

Background Insulin resistance, hyperinsulinemia, and myocardial hypert rophy frequently coexist in patients. Whether hyperinsulinemia directl y affects myocardial protein metabolism in humans has not been examine d, however. To test the hypothesis that hyperinsulinemia is anabolic f or human heart protein, we examined the effects of insulin infusion on myocardial dial protein synthesis, degradation, and net balance in pa tients with ischemic heart disease. Methods and Results Eleven men (ag ed 57+/-3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU . m(-2). min( -1)) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilut ion of L-[ring-2,6-H-3]phenylalanine across the heart basally and 90 m inutes into infusion. Subjects had elevated fasting plasma insulin con centrations (173+/-21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degrad ation, as estimated by phenylalanine release (133+/-28 nmol/min), exce eded protein synthesis, estimated by phenylalanine uptake (31+/-15 nmo l/min), resulting in net negative phenylalanine balance (-102+/-17 nmo l/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine bal ance to neutral. Conclusions Acute hyperinsulinemia markedly suppresse s myocardial protein degradation in patients with cardiovascular disea se who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hyp ertrophy in patients with cardiovascular disease.