Identification and Characterization of an Exercise-sensitive Pool of Glucose Transporters in Skeletal Muscle

Abstract

Augmentation of glucose transport into skeletal muscle by GLUT4 translocation to the plasma and T-tubule membranes can be mediated independently by insulin and by contraction/exercise. Available data suggest that separable pools of intracellular GLUT4 respond to these two stimuli. To identify and characterize these pools, we fractionated skeletal muscle membranes in a discontinuous sucrose density gradient. Fractions of 32 and 36% sucrose exhibited the highest enrichment of GLUT4 and were independently responsive to insulin and exercise, respectively. The combination of the two stimuli depleted both GLUT4 fractions simultaneously. Both vesicle populations contained the gp160 aminopeptidase, whose expression had previously been shown to be specific to muscle and fat and restricted to GLUT4 vesicles in the latter tissue. In muscle, gp160 translocates exactly as does GLUT4 in response to insulin and exercise. The contraction- and insulin-sensitive GLUT4 pools also contained secretory component-associated membrane protein/glucose transporter vesicle triplet but not GLUT1 and caveolin. Immunoadsorption of the two pools followed by silver staining did not reveal any obvious difference in their major protein components. On the other hand, sedimentational analysis in sucrose velocity gradients revealed that the insulin-sensitive GLUT4 vesicles had a larger sedimentation coefficient than the exercise-sensitive vesicles. Thus, the separation of the two intracellular GLUT4 pools should be useful in dissecting what are likely to be different signal transduction pathways that mediate their translocation to the cell surface.

Circulating soluble transferrin receptor concentration decreases after exercise-induced improvement of insulin sensitivity in obese individuals

“…Contracting myofibers need to obtain glucose very rapidly to cope with the energy demands that increase dramatically when contraction is initiated. Coderre et al 9 reported the isolation of distinct insulin-and exercise-sensitive GLUT4 intracellular pools. Interestingly, the transferrin receptor defines two distinct contraction and insulin-responsive GLUT4 vesicle populations in in vitro studies on skeletal muscles.…”

Differences in Signaling Properties of the Cytoplasmic Domains of the Insulin Receptor and Insulin-like Growth Factor Receptor in 3T3-L1 Adipocytes

“…This result implies that the IR signals to a larger intracellular pool of transporters than the IGFR, which might reflect differential efficiency of mobilization from a single pool of transporters, or differential recruitment from more than one pool. In relation to the latter possibility, it has been shown that GLUT4 vesicles cycle through several distinct intracellular compartments in adipocytes (40), and in skeletal muscle, discrete pools of GLUT4 vesicles are responsive to stimulation by insulin and contraction (41).…”

Activation of the ERK Pathway and Atypical Protein Kinase C Isoforms in Exercise- and Aminoimidazole-4-carboxamide- 1-β-d-riboside (AICAR)-stimulated Glucose Transport

“…The mechanism for this insulin-like effect of exercise on glucose transport is only partly understood. Like insulin, exercise increases the translocation of Glut4 glucose transporters to the plasma membrane in skeletal muscle; however, these exercise-regulated glucose transporters may largely exist in functional pools different from those mobilized by insulin (1). Also, unlike insulin, exercise activates Glut4 translocation/glucose transport in skeletal muscle by a mechanism that does not involve the activation of phosphatidylinositol (PI) 1 3-kinase (2).…”

“…Like insulin, exercise increases the translocation of Glut4 glucose transporters to the plasma membrane in skeletal muscle; however, these exercise-regulated glucose transporters may largely exist in functional pools different from those mobilized by insulin (1). Also, unlike insulin, exercise activates Glut4 translocation/glucose transport in skeletal muscle by a mechanism that does not involve the activation of phosphatidylinositol (PI) 1 3-kinase (2). Instead, exercise stimulates Glut4 translocation/glucose transport by a mechanism thought to be at least partly dependent upon ATP breakdown, leading to increases in 5Ј-AMP and activation of 5Ј-AMP-activated protein kinase, AMPK (2).…”