Roles of Insulin-Like Growth Factor-1 in Muscle Wasting and Osteopenia in Mice with Hyponatremia.

Abstract

Hyponatremia is associated with sarcopenia and osteoporosis in elderly individuals. Skeletal muscle releases myokines, which affect distant organs, including bone. However, the detailed mechanisms by which hyponatremia influences muscle and bone remain unclear. We herein investigated the effects of hyponatremia on muscle, bone, and myokines linking muscle to bone in mice treated with 1-desamino-8-D-arginine vasopressin (dDAVP) or furosemide, which induce hyponatremia. Muscle mass and bone mineral density (BMD) were analyzed 8 weeks after the administration of dDAVP or furosemide. dDAVP significantly reduced grip strength, but did not affect tissue weights of gastrocnemius or soleus muscles of mice. Furosemide significantly decreased muscle mass, tissue weights of gastrocnemius and soleus muscles, and grip strength in mice. dDAVP and furosemide decreased trabecular BMD, trabecular bone volume, and cortical BMD at the femurs. Among myokines linking muscle to bone, hyponatremia reduced expression of insulin-like growth factor (IGF)-1 in gastrocnemius and soleus muscles and serum IGF-1 levels in mice. In simple regression analyses, serum IGF-1 levels were positively related to muscle IGF-1 expression, trabecular bone volume, and cortical BMD in mice. The administration of sodium chloride solution to mice ameliorated the decreases in grip strength, muscle mass, trabecular bone volume, cortical BMD, and the levels of muscle and circulating IGF-1 in furosemide-treated mice. The present study demonstrated that hyponatremia induces muscle and bone loss as well as a decrease in muscle IGF-1 expression in mice. The present findings suggest that IGF-1 might be related to muscle wasting and bone loss induced by hyponatremia in mice.