title: Insulin-mediated translocation of GLUT-4-containing vesicles is preserved in denervated muscles.
abstract: Skeletal muscle denervation decreases insulin-sensitive glucose uptake into this tissue as a result of marked GLUT-4 protein downregulation ( approximately 20% of controls). The process of insulin-stimulated glucose transport in muscle requires the movement or translocation of intracellular GLUT-4-rich vesicles to the cell surface, and it is accompanied by the translocation of several additional vesicular cargo proteins. Thus examining GLUT-4 translocation in muscles from denervated animals allows us to determine whether the loss of a major cargo protein, GLUT-4, affects the insulin-dependent behavior of the remaining cargo proteins. We find no difference, control vs. denervated, in the insulin-dependent translocation of the insulin-responsive aminopeptidase (IRAP) and the receptors for transferrin and insulin-like growth factor II/mannose 6-phosphate, proteins that completely (IRAP) or partially co-localize with GLUT-4. We conclude that 1) denervation of skeletal muscle does not block the specific branch of insulin signaling pathway that connects receptor proximal events to intracellular GLUT-4-vesicles, and 2) normal levels of GLUT-4 protein are not necessary for the structural organization and insulin-sensitive translocation of its cognate intracellular compartment. Muscle denervation also causes a twofold increase in GLUT-1. In normal muscle, all GLUT-1 is present at the cell surface, but in denervated muscle a significant fraction (25.1 +/- 6.1%) of this transporter is found in intracellular vesicles that have the same sedimentation coefficient as GLUT-4-containing vesicles but can be separated from the latter by immunoadsorption. These GLUT-1-containing vesicles respond to insulin and translocate to the cell surface. Thus the formation of insulin-sensitive GLUT-1-containing vesicles in denervated muscle may be a compensatory mechanism for the decreased level of GLUT-4.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.forename: G
authors.initials: G
authors.lastname: Vallega
authors.forename: K V
authors.initials: KV
authors.lastname: Kandror
authors.forename: P F
authors.initials: PF
authors.lastname: Pilch
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009121:Muscle Denervation; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat