title: Mechanisms in exercise-induced increase in glucose disposal in skeletal muscle.
abstract: This chapter reviews current knowledge of the various signaling pathways that cause the glucose transporter isoform 4 (GLUT4)-containing vesicles to translocate from intracellular compartments of skeletal muscle cells to the plasma membrane in response to exercise. Specifically, the signaling cascades that arise from increases in AMP (adenosine monophosphate), nitric oxide (NO) and calcium (Ca2+) are described. Evidence is provided that these signaling pathways converge with the insulin signaling cascade at: (a) aPKC (atypical protein kinase C), which signals via GTPases to remodel microtubules along which GLUT4-containing vesicles translocate, and (b) AS160 (a 160-kDa Akt substrate that has Rab-GTPase activity) to activate microtubule motor kinesin proteins that power vesicle translocation. Experimental evidence showing that joint activation of AS160 and aPKC pathways are necessary for GLUT4 mobilization to the cell surface is given along with evidence of overlap between Ca2+, NO and AMP-dependent protein kinase-signaling pathways. The chapter also describes the molecular mechanisms by which exercise increases GLUT4 expression to boost glucose disposal capacity of skeletal muscle.
authors.affiliation: UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Edward O
authors.initials: EO
authors.lastname: Ojuka
authors.forename: Veeraj
authors.initials: V
authors.lastname: Goyaram
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009569:Nitric Oxide; D000249:Adenosine Monophosphate; D005947:Glucose; D002118:Calcium