Interaction of physiological mechanisms in control of muscle glucose uptake.

1. Control of glucose uptake is distributed between three steps. These are the rate that glucose is delivered to cells, the rate of transport into cells, and the rate that glucose is phosphorylated within these same cells. The functional limitations to each one of these individual steps has been difficult to assess because they are so closely coupled to each other. Studies have been performed in recent years using complex isotopic techniques or transgenic mouse models to shed new light on the role that each step plays in overall control of muscle glucose uptake. 2. Membrane glucose transport is a major barrier and glucose delivery and glucose phosphorylation are minor barriers to muscle glucose uptake in the fasted, sedentary state. GLUT-4 is translocated to the muscle membrane during exercise and insulin-stimulation. The result of this is that it can become so permeable to glucose that it is only a minor barrier to glucose uptake. 3. In addition to increasing glucose transport, exercise and insulin-stimulation also increase muscle blood flow and capillary recruitment. This effectively increases muscle glucose delivery and by doing so, works to enhance muscle glucose uptake. 4. There is a growing body of data that suggests that insulin resistance to muscle glucose uptake can be because of impairments in any one or more of the three steps that comprise the process.