Abstract
Exercise increases glucose uptake in skeletal muscle independently of insulin signaling. This makes exercise an effective stimulus to increase glucose uptake in insulin-resistant skeletal muscle. AMPK has been suggested to regulate muscle glucose uptake during exercise/contraction, but findings from studies of various AMPK transgenic animals have not reached consensus on this matter. Comparing methods used in these studies reveals a hitherto unappreciated difference between those studies reporting a role of AMPK and those that do not. This led us to test the hypothesis that AMPK and downstream target TBC1D1 are involved in regulating muscle glucose uptake in the immediate period after exercise/contraction but not during exercise/contraction. Here we demonstrate that glucose uptake during exercise/contraction was not compromised in AMPK-deficient skeletal muscle, whereas reversal of glucose uptake toward resting levels after exercise/contraction was markedly faster in AMPK-deficient muscle compared with wild-type muscle. Moreover, muscle glucose uptake after contraction was positively associated with phosphorylation of TBC1D1, and skeletal muscle from TBC1D1-deficient mice displayed impaired glucose uptake after contraction. These findings reconcile previous observed discrepancies and redefine the role of AMPK activation during exercise/contraction as being important for maintaining glucose permeability in skeletal muscle in the period after, but not during, exercise/contraction.