Paige C. Geiger, Ph.D.

Insulin and muscle contractile activity induce skeletal muscle glucose transport through distinct signaling pathways. Insulin-mediated glucose transport involves phosphorylation of the insulin receptor and insulin receptor substrate-1 and-2 on tyrosine residues, and the activation of phosphatidylinositide 3-kinase (PI3-kinase). In contrast, contraction-mediated glucose transport is thought to occur through intracellular signaling involving Ca2+/calmodulin-dependent protein kinase and 5’AMP-activated protein kinase. GLUT 4 is the major glucose transport isoform in skeletal muscle and translocation of GLUT4 from inside the cell to the plasma membrane is the major mechanism by which both insulin and muscle contractions increase glucose transport. While insulin stimulated glucose transport is impaired in individuals with type II diabetes, contraction induced glucose transport is not. As a result, exercise functions as a clinically relevant alternative pathway for glucose disposal in conditions of insulin resistance.

Glucose transport system in skeletal muscle