Insulin-induced membrane permeability to glucose in human muscles at rest and following exercise
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Insulin-induced membrane permeability to glucose in human muscles at rest and following exercise. / McConell, Glenn Kevin; Sjøberg, Kim Anker; Ceutz, Frederik; Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva; Frøsig, Christian; Kiens, Bente; Wojtaszewski, Jørgen; Richter, Erik A.
In: Journal of Physiology, Vol. 598, No. 2, 2020, p. 303-315.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Insulin-induced membrane permeability to glucose in human muscles at rest and following exercise
AU - McConell, Glenn Kevin
AU - Sjøberg, Kim Anker
AU - Ceutz, Frederik
AU - Gliemann, Lasse
AU - Nyberg, Michael Permin
AU - Hellsten, Ylva
AU - Frøsig, Christian
AU - Kiens, Bente
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
N1 - This article is protected by copyright. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Increased insulin action is an important component of the health benefits of exercise, but the regulation of insulin action in vivo is complex and not fully elucidated. Increases in skeletal muscle insulin-stimulated GLUT4 translocation are inconsistent and mostly cannot explain the increases in insulin action in humans. Here we used leg glucose uptake (LGU) and interstitial muscle glucose concentration to calculate insulin-induced muscle membrane permeability to glucose, a variable not previously possible to quantify in humans. Muscle membrane permeability to glucose, measured 4 h after one-legged knee-extensor exercise, increased ∼17-fold during a submaximal euglycaemic hyperinsulinaemic clamp in rested muscle (R) and ∼36-fold in exercised muscle (EX). Femoral arterial infusion of L-NMMA or ATP decreased and increased, respectively, leg blood flow (LBF) in both legs but did not affect membrane glucose permeability. Decreasing LBF reduced interstitial glucose concentrations to ∼2 mM in the exercised but only to ∼3.5 mM in non-exercised muscle and abrogated the augmented effect of insulin on LGU in the EX leg. Increasing LBF by ATP infusion increased LGU in both legs with uptake higher in the EX leg. We conclude that it is possible to measure functional muscle membrane permeability to glucose in humans and it increases twice as much in exercised vs. rested muscle during submaximal insulin stimulation. We also show that muscle perfusion is an important regulator of muscle glucose uptake when membrane permeability to glucose is high and we show that the capillary wall can be a significant barrier for glucose transport.
AB - Increased insulin action is an important component of the health benefits of exercise, but the regulation of insulin action in vivo is complex and not fully elucidated. Increases in skeletal muscle insulin-stimulated GLUT4 translocation are inconsistent and mostly cannot explain the increases in insulin action in humans. Here we used leg glucose uptake (LGU) and interstitial muscle glucose concentration to calculate insulin-induced muscle membrane permeability to glucose, a variable not previously possible to quantify in humans. Muscle membrane permeability to glucose, measured 4 h after one-legged knee-extensor exercise, increased ∼17-fold during a submaximal euglycaemic hyperinsulinaemic clamp in rested muscle (R) and ∼36-fold in exercised muscle (EX). Femoral arterial infusion of L-NMMA or ATP decreased and increased, respectively, leg blood flow (LBF) in both legs but did not affect membrane glucose permeability. Decreasing LBF reduced interstitial glucose concentrations to ∼2 mM in the exercised but only to ∼3.5 mM in non-exercised muscle and abrogated the augmented effect of insulin on LGU in the EX leg. Increasing LBF by ATP infusion increased LGU in both legs with uptake higher in the EX leg. We conclude that it is possible to measure functional muscle membrane permeability to glucose in humans and it increases twice as much in exercised vs. rested muscle during submaximal insulin stimulation. We also show that muscle perfusion is an important regulator of muscle glucose uptake when membrane permeability to glucose is high and we show that the capillary wall can be a significant barrier for glucose transport.
KW - Faculty of Science
KW - Insulin sensitivity
KW - Microdialysis
KW - Glucose uptake
U2 - 10.1113/JP278600
DO - 10.1113/JP278600
M3 - Journal article
C2 - 31696935
VL - 598
SP - 303
EP - 315
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 2
ER -
ID: 229899780