title: Mechanisms by which insulin and muscle contraction stimulate glucose transport.
abstract: Insulin binding to its receptor activates a tyrosine kinase that initiates a cascade of signaling events, the initial step being the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Subsequent IRS-1 association and activation of phosphatidylinositiol 3-kinase (PI 3-kinase) is believed to be involved in the events leading to the translocation of glucose transporters (GLUT4) to the plasma membrane resulting in uptake of glucose into the cell. Muscle contractions increase insulin sensitivity, but also stimulate muscle glucose uptake independent of insulin. The contraction signaling pathway is distinct from the insulin pathway because the effect of insulin and contractions on glucose uptake are additive, and contractions do not increase insulin receptor kinase or PI 3-kinase activity. In contrast, studies indicating that contractions cause the translocation of GLUT4 and that both contractions and insulin-stimulated glucose transport can be blocked by calcium channel blockers suggest that the two pathways may converge. However, the possibility that two distinct GLUT4 pools may be targeted, one by insulin the other by contractions, indicates that additional research is needed to better define the mechanisms by which glucose transport is stimulated in muscle.
authors.affiliation: Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Cortright
authors.forename: G L
authors.initials: GL
authors.lastname: Dohm
mesh_terms: D000818:Animals; D001692:Biological Transport; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism
chemical_list: D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005947:Glucose