| Research Abstract |
Exercise is a potent stimulator of glucose metabolism in skeletal muscle. AMPK is a heterotrimeric protein consisting of catalytic α and regulatory β and γ subunits, and is rapidly activated in response to exercise in skeletal muscle. The main purpose of the present study was to determine if contraction-stimulated AMPK plays a role in regulating muscle glucose metabolism. Mammalian skeletal muscle expresses two distinct α isoforms: α1 and α2. Supraphysiological contraction, such as tetanic contraction by electromyostimulation, activated both α1 and α2, but moderate-intensity exercise such as treadmill running selectively activated α2 in rat skeletal muscle. α2 activity was increased in an exercise intensity- and duration-dependent manner, in parallel with insulin-independent glucose transport activity. Furthermore, pharmacological inhibition of α2 significantly inhibited contraction-stimulated glucose transport in rat muscles in vitro. Similar to the observations of animal muscles, end
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urance exercise (= 70 %VO2max) that had been shown to activate glucose transport stimulated α2, but not α1 in human skeletal muscle. Pharmacological α-2 activation by intraperitoneal or subcutaneous injection of AICAR activated glucose transport in mouse skeletal muscle, to a similar extent that was achieved in response to moderate-intensity exercise. In addition, similar to the effect of chronic exercise training, repeated injections of AICAR for 4-7 days significantly increased glucose transporter GLUT4 in mouse skeletal muscle. These results suggest that AMPKα2 is a signaling intermediary leading to exercise-stimulated glucose transport and GLUT4 expression, while AMPK does not seem to play a major role in exercise-stimulated glycogen metabolism in skeletal muscle. When rat muscles were incubated in the presence of thiazolidinediones, widely prescribed antidiabetic reagents, α2 was significantly stimulated in parallel with insulin-independent glucose transport activity. In addition to the conventional effect of increasing insulin sensitivity, thiazolidinediones may have an exercise-like effect on skeletal muscle glucose transport via AMPK-dependent mechanism. Less
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