AMPK and TBC1D1 regulate muscle glucose uptake after, but not during, exercise and contraction
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AMPK and TBC1D1 regulate muscle glucose uptake after, but not during, exercise and contraction. / Kjøbsted, Rasmus; Roll, Julie Louise Weinreich; Jørgensen, Nicolas Oldenburg; Birk, Jesper Bratz; Foretz, Marc; Viollet, Benoit; Chadt, Alexandra; Al-Hasani, Hadi; Wojtaszewski, Jørgen.
In: Diabetes, Vol. 68, No. 7, 2019, p. 1427-1440.Research output: Contribution to journal › Journal article › Research › peer-review
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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 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 to 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 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 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 to 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 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
VL - 68
SP - 1427
EP - 1440
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -
ID: 216875307