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

Abstract

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<0.05). However, no significant circulating musclin level between sedentary and exercised diabetic rats was observed. In contrast, aerobic exercise training in the diabetic rats induced elevation of QUICKI and reduction of cfPWV, serum insulin, muscle musclin, and arterial NPR-C levels (each p<0.05). NPR-C protein level was positively correlated with cfPWV (r=0.43, p=0.09). Additionally, muscle musclin levels was significantly negatively correlated with muscle GLUT4 translocation (r=-0.78, p<0.01) and QUICKI (r=-0.82, p<0.01). 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.