Musclin Regulates Glucose Uptake in Human Skeletal Muscle Cells via Insulin-Independent pathway

Abstract

Exercise is considered as the most effective therapeutic strategy in the improvement of metabolic diseases. Skeletal muscle is involved in the homeostasis of energy metabolism via its secretory proteins known as myokines, thereby (skeletal muscle is) considered as an endocrine organ. Musclin (osteocrin) is one of the putative myokines, and its roles in lipid metabolism have been previously suggested. However, its physiological mechanism has not been elucidated. Recently, G-protein coupled receptor 1 (GPR1) has been reported to have a binding site for musclin. By considering that GPR1 is coupled to Gαq/11 and Gαs, we hypothesized that musclin exerts its physiological effects via Ca2+- or cyclic AMP-dependent pathways. We investigated the effects of musclin on glucose metabolism in primary human skeletal muscle cells. Musclin increased Akt phosphorylation on Thr308 and Ser473. Besides, it increased phosphorylation on Ser2481 of mTORC2, thereby, stimulated glucose transporter type 4 (GLUT4) translocation. Musclin increased intracellular cyclic AMP (cAMP) levels which are responsible for the activation of Akt at Ser473 through mTORC2. These effects remain unclear whether GPR1 was related. In conclusion, our study demonstrated that musclin promotes glucose uptake in primary human skeletal muscle cells via insulin-independent pathway and suggested that musclin, as a myokine, represents exercise-induced improvement of glucose metabolism.