Abstract 17235: Attenuation of NPR-C Binding With Muscle-Derived Musclin is Related to Reduced Cardiovascular Disease Risks by Aerobic Exercise Training in Type 2 Diabetic Rats

Introduction: Aerobic exercise training (AT) in type 2 diabetic patients reduces cardiovascular disease (CVD) risks, such as an impairment of NO-derived vasodilation mediated by obese and hyperinsulinemia. Musclin is a muscle-derived myokine and binds to natriuretic peptide receptor-C (NPR-C). Elevation of circulating musclin level deteriorates of insulin resistance. Furthermore, musclin-induced vasocontraction mediated by NPR-C leads to increase in blood pressures. However, the effect of AT on muscle-derived musclin secretion in type 2 diabetes remains unclear. Hypothesis: This study aimed to clarify whether AT-induced attenuations of muscle-derived musclin secretion and arterial NPR-C expression levels are related to reduction of CVD risks in type 2 diabetes rats. Methods: Twenty 20-week-old male type 2 diabetic (OLETF) rats were randomly divided into two groups; 8-week sedentary control and aerobic exercise training (treadmill running for 60min at 25m/min, 5days/week) (n=7 each group) and seven male LETO rats used as healthy sedentary control. After 8 weeks, we measured carotid-femoral pulse wave velocity (cfPWV, an index of arterial stiffness), QUICKI (an index of insulin sensitivity), plasma and muscle musclin levels and GLUT4 translocation levels, arterial NPR-C protein expression. Results: In sedentary diabetic rats, cfPWV, serum insulin and muscle musclin levels, and arterial NPR-C protein expression increased, and QUICKI decreased as compared to healthy sedentary rats (each p Conclusions: These results suggest that attenuation of arterial NPR-C expression and muscle-derived musclin secretion is related to reductions of arterial stiffness and hyperinsulinemia by AT in type 2 diabetic rats.