TY - JOUR

T1 - Insulin sensitization following a single exercise bout is uncoupled to glycogen in human skeletal muscle: A meta-analysis of 13 single-center human studies

AU - Hingst, Janne Rasmuss

AU - Onslev, Johan Dejgaard

AU - Holm, Stephanie

AU - Kjøbsted, Rasmus

AU - Frøsig, Christian

AU - Kido, Kohei

AU - Steenberg, Dorte Enggaard

AU - Larsen, Magnus Romme

AU - Kristensen, Jonas Møller

AU - Carl, Christian Strini

AU - Sjøberg, Kim

AU - Thong, Farah S L

AU - Derave, Wim

AU - Pehmøller, Christian

AU - Brandt, Nina

AU - McConell, Glenn

AU - Jensen, Jørgen

AU - Kiens, Bente

AU - Richter, Erik A.

AU - Wojtaszewski, Jørgen

N1 - © 2022 by the American Diabetes Association.

PY - 2022

Y1 - 2022

N2 - Exercise profoundly influences glycemic control by enhancing muscle insulin sensitivity, thus promoting glucometabolic health. While prior glycogen breakdown so far has been deemed integral for muscle insulin sensitivity to be potentiated by exercise, the mechanisms underlying this phenomenon remain enigmatic. We have combined original data from 13 of our studies that investigated insulin action in skeletal muscle either under rested conditions or following a bout of one-legged knee extensor exercise in healthy young male individuals (n = 106). Insulin-stimulated glucose uptake was potentiated and occurred substantially faster in the prior contracted muscles. In this otherwise homogenous group of individuals, a remarkable biological diversity in the glucometabolic responses to insulin is apparent both in skeletal muscle and at the whole-body level. In contrast to the prevailing concept, our analyses reveal that insulin-stimulated muscle glucose uptake and the potentiation thereof by exercise are not associated with muscle glycogen synthase activity, muscle glycogen content, or degree of glycogen utilization during the preceding exercise bout. Our data further suggest that the phenomenon of improved insulin sensitivity in prior contracted muscle is not regulated in a homeostatic feedback manner from glycogen. Instead, we put forward the idea that this phenomenon is regulated by cellular allostatic mechanisms that elevate the muscle glycogen storage set point and enhance insulin sensitivity to promote the uptake of glucose toward faster glycogen resynthesis without development of glucose overload/toxicity or feedback inhibition.

AB - Exercise profoundly influences glycemic control by enhancing muscle insulin sensitivity, thus promoting glucometabolic health. While prior glycogen breakdown so far has been deemed integral for muscle insulin sensitivity to be potentiated by exercise, the mechanisms underlying this phenomenon remain enigmatic. We have combined original data from 13 of our studies that investigated insulin action in skeletal muscle either under rested conditions or following a bout of one-legged knee extensor exercise in healthy young male individuals (n = 106). Insulin-stimulated glucose uptake was potentiated and occurred substantially faster in the prior contracted muscles. In this otherwise homogenous group of individuals, a remarkable biological diversity in the glucometabolic responses to insulin is apparent both in skeletal muscle and at the whole-body level. In contrast to the prevailing concept, our analyses reveal that insulin-stimulated muscle glucose uptake and the potentiation thereof by exercise are not associated with muscle glycogen synthase activity, muscle glycogen content, or degree of glycogen utilization during the preceding exercise bout. Our data further suggest that the phenomenon of improved insulin sensitivity in prior contracted muscle is not regulated in a homeostatic feedback manner from glycogen. Instead, we put forward the idea that this phenomenon is regulated by cellular allostatic mechanisms that elevate the muscle glycogen storage set point and enhance insulin sensitivity to promote the uptake of glucose toward faster glycogen resynthesis without development of glucose overload/toxicity or feedback inhibition.

KW - Humans

KW - Male

KW - Insulin/metabolism

KW - Glycogen/metabolism

KW - Glycogen Synthase/metabolism

KW - Insulin Resistance/physiology

KW - Isophane Insulin, Human

KW - Muscle, Skeletal/metabolism

KW - Glucose/metabolism

KW - Insulin, Regular, Human

KW - Muscle glycogen storage

KW - Insulin sensitivity

KW - Uptake of glucose

KW - Glycogen resynthesis

U2 - 10.2337/db22-0015

DO - 10.2337/db22-0015

M3 - Journal article

C2 - 36265014

VL - 71

SP - 2237

EP - 2250

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -