Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity.
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.
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen, Denmark.|Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2100, Copenhagen, Denmark.
Rasmus
R
Kjøbsted
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2100, Copenhagen, Denmark.
Jørgen F P
JF
Wojtaszewski
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen, Denmark. jttreebak@sund.ku.dk.
Jonas T
JT
Treebak
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D015444:Exercise; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009119:Muscle Contraction / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology*; D055503:Protein Multimerization; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D021122:Protein Subunits; D012265:Ribonucleotides; C526441:TBC1D1 protein, human; C518767:TBC1D4 protein, human; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; D006003:Glycogen; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose
AMP-activated protein kinase; AS160; Exercise; Glucose uptake; Insulin sensitivity; Skeletal muscle; TBC1D4