A cellular model of depolarization‐regulated GLUT4 exocytosis and endocytosis in muscle cells

Skeletal muscle increases its glucose uptake during exercise (muscle contraction). Numerous physiological and metabolic changes are associated with muscle contraction, from membrane depolarization (MD) to increased energy demand. We hypothesize that MD elicits signals that stimulate glucose uptake into muscle during contraction. Accordingly, we used L6 muscle cell stably expressing myc‐tagged GLUT4 but lacking sarcomeres, to study the effects of MD independently of an ensuing contraction. K‐induced MD elevated glucose uptake and cell‐surface associated glucose transporter GLUT4. This gain arose from a reduction in the rate of GLUT4 internalization, with a minute increase in the rate of GLUT4 externalization. MD increased intracellular free calcium levels. The increase in surface GLUT4 in response to MD was completely abolished by intracellular calcium chelation and by three distinct protein kinase C (PKC) inhibitors at concentrations that inhibit conventional PKC isoforms. In contrast, siRNA to alpha1,2 AMPK did prevent the surface gain in GLUT4. Thus, we propose that the MD‐induced GLUT4 retention at plasma membrane may be mediated by conventional PKCs. This work was supported by the Canadian Diabetes Association