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

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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.

Original languageEnglish
Issue number11
Pages (from-to)2237-2250
Number of pages14
Publication statusPublished - 2022

Bibliographical note

© 2022 by the American Diabetes Association.

    Research areas

  • Humans, Male, Insulin/metabolism, Glycogen/metabolism, Glycogen Synthase/metabolism, Insulin Resistance/physiology, Isophane Insulin, Human, Muscle, Skeletal/metabolism, Glucose/metabolism, Insulin, Regular, Human, Muscle glycogen storage, Insulin sensitivity, Uptake of glucose, Glycogen resynthesis

ID: 323608717