Mechanism of skeletal muscle contraction: Role of mechanical muscle contraction in glucose homeostasis

Abstract

Physical exercise has beneficial effects on whole-body glucose homeostasis and reduces the risk of metabolic diseases such as obesity, diabetes, and insulin resistance. Muscle contraction increases glucose uptake by skeletal muscle cells via an insulin-independent signaling mechanism. There is an increasing evidence that contraction-induced glucose uptake is mediated by AMP-activated protein kinase (AMPK), an energy sensor in skeletal muscle. Recent studies have identified another signaling pathway involving sucrose nonfermenting AMPK-related kinase that is activated by muscle contraction. Acute muscle contraction also activates insulin-induced glucose transport, and TBC1D4 has been identified as a regulator of insulin sensitization. Increased lipid oxidation and utilization resulting from chronic muscle contraction can stimulate insulin-induced glucose transport, since tissue accumulation of lipid metabolites—that is, lipotoxicity—is a basis for insulin resistance. Carnitine also normalizes intracellular lipid state by buffering excess accumulation of acetyl coenzyme A, a potent inhibitor of key enzymes in glucose metabolism. Finally, chronic exercise affects not only skeletal muscle but also pancreatic function and enhances insulin secretion. The current knowledge regarding the mechanism of glucose uptake induced by muscle contraction is summarized in this chapter.