Role for the Microvasculature in Glucose Uptake in Skeletal Muscle

Skeletal muscle is an important site for insulin action and is responsible for ~80% of insulin-mediated glucose disposal following a meal. Insulin stimulates muscle glucose uptake in two ways: firstly insulin improves the delivery of glucose to muscle cells by increasing blood flow to the microvasculature and transport across the endothelium in contact with the myocyte, and secondly by increasing glucose uptake across the muscle cell membrane via activation of the insulin signalling pathway leading to the recruitment of a specific glucose transporter (GLUT4) to the cell membrane. During insulin resistance and type 2 diabetes, both of these responses to insulin can become impaired. Here we review the considerable body of literature showing that insulin-stimulated microvascular recruitment improves the delivery of insulin and glucose to the myocyte to augment insulin’s metabolic action, and that vascular actions of insulin are lost during insulin resistance and type 2 diabetes. Furthermore we discuss more recent evidence to suggest that microvascular insulin responses are lost prior to and independently of the development of myocyte insulin resistance.