AMPK and TBC1D1 regulate muscle glucose uptake after, but not during, exercise and contraction

TY - JOUR

T1 - AMPK and TBC1D1 regulate muscle glucose uptake after, but not during, exercise and contraction

AU - Kjøbsted, Rasmus

AU - Roll, Julie Louise Weinreich

AU - Jørgensen, Nicolas Oldenburg

AU - Birk, Jesper Bratz

AU - Foretz, Marc

AU - Viollet, Benoit

AU - Chadt, Alexandra

AU - Al-Hasani, Hadi

AU - Wojtaszewski, Jørgen

N1 - CURIS 2019 NEXS 219 © 2019 by the American Diabetes Association.

PY - 2019

Y1 - 2019

N2 - Exercise increases glucose uptake in skeletal muscle independently of insulin signaling. This makes exercise an effective stimulus to increase glucose uptake in insulinresistant skeletal muscle. AMPK has been suggested to regulate muscle glucose uptake during exercise/contraction, but findings fromstudies 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 AMPKdeficient 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.

AB - Exercise increases glucose uptake in skeletal muscle independently of insulin signaling. This makes exercise an effective stimulus to increase glucose uptake in insulinresistant skeletal muscle. AMPK has been suggested to regulate muscle glucose uptake during exercise/contraction, but findings fromstudies 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 AMPKdeficient 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.

KW - Faculty of Science

KW - Glucose transport

KW - Exercise metabolism

KW - Glucose homeostasis

KW - AMP-activated protein kinase

KW - Exercise recovery

U2 - 10.2337/db19-0050

DO - 10.2337/db19-0050

M3 - Journal article

C2 - 31010958

SN - 0012-1797

VL - 68

SP - 1427

EP - 1440

JO - Diabetes

JF - Diabetes

IS - 7

ER -