Insulin-mediated translocation of GLUT-4-containing vesicles is preserved in denervated muscles

• Published in: American journal of physiology: endocrinology and metabolism 2000-06, Vol.278 (6), p.E1019-E1026
• Main Authors: Zhou, Min, Vallega, Gino, Kandror, Konstantin V, Pilch, Paul F
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - drug effects; Cell Fractionation; Cell Membrane - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 4; Insulin - pharmacology; Male; Monosaccharide Transport Proteins - metabolism; Muscle Denervation; Muscle Proteins; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Rats; Rats, Sprague-Dawley; Sciatic Nerve
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.2000.278.6.e1019

Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 Skeletal muscle denervation decreases insulin-sensitive glucose uptake into this tissue as a result of marked GLUT-4 protein downregulation (~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. denervation; rats; skeletal muscle