Abstract
Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis. A single bout of exercise has long been known to increase glucose disposal in skeletal muscle in response to physiological insulin concentrations. While this effect is identified to be restricted to the previously exercised muscle, the molecular basis for an apparent convergence between exercise- and insulin-induced signaling pathways is incompletely known. In recent years, we and others have identified the Rab GTPase-activating protein, TBC1 domain family member 4 (TBC1D4) as a target of key protein kinases in the insulin- and exercise-activated signaling pathways. Our working hypothesis is that the AMP-activated protein kinase (AMPK) is important for the ability of exercise to insulin sensitize skeletal muscle through TBC1D4. Here, we aim to provide an overview of the current available evidence linking AMPK to post-exercise insulin sensitivity.
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Acknowledgements
Jesper B. Birk and Rasmus Quistgaard are acknowledged for skilled technical assistance at experiments presented in Figs. 5.1 and 5.2, respectively. RK and JTT were supported by the Novo Nordisk Foundation Center for Basic Metabolic Research. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://metabol.ku.dk). RK was also supported by Department of Nutrition, Exercise and Sports, University of Copenhagen. JFPW and the studies presented in this chapter were supported by the Danish Council for Independent Research | Medical Sciences, the Novo Nordisk Foundation, The Lundbeck Foundation, and The research program “Physical activity and nutrition for improvement of health” funded by the University of Copenhagen Excellence Program for Interdisciplinary Research. Some paragraphs from this text are in part based on a Ph.D. thesis written by RK.
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Kjøbsted, R., Wojtaszewski, J.F.P., Treebak, J.T. (2016). Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity. In: Cordero, M., Viollet, B. (eds) AMP-activated Protein Kinase. Experientia Supplementum, vol 107. Springer, Cham. https://doi.org/10.1007/978-3-319-43589-3_5
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