Role of the AMPKγ3 isoform in hypoxia-stimulated glucose transport in glycolytic skeletal muscle

Skeletal muscle glucose transport is regulated via the canonical insulin-signaling cascade as well as by energy-sensing signals. 5′-AMP-activated protein kinase (AMPK) has been implicated in the energy status regulation of glucose transport. We determined the role of the AMPKγ3 isoform in hypoxia-mediated energy status signaling and glucose transport in fast-twitch glycolytic extensor digitorum longus (EDL) muscle from AMPKγ3-knockout (KO) mice and wild-type mice. Although hypoxia increased glucose transport (P < 0.001) in wild-type mice, this effect was attenuated in AMPKγ3-KO mice (45% reduction, P < 0.01). The role of Ca2+-mediated signaling was tested using the Ca2+/calmodulin competitive inhibitor KN-93. KN-93 exposure reduced hypoxia-mediated glucose transport in AMPKγ3-KO and wild-type mice (P < 0.05). To further explore the underlying signaling mechanisms, phosphorylation of CaMKII, AMPK, ACC, and TBC1D1/D4 as well as isoform-specific AMPK activity was determined. Basal and hypoxia-mediated phosph...