Invited Symposium: Intracellular Traffic of Organelles



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Intracellular Traffic of GLUT4 Glucose Trnasporter in Skeletal Muscle

Dombrowski, L. (CRML, Laval University Hospital Research Center, Canada)
Faure, R. (Neuroscience Unit, Laval University Hospital Research Center, Canada)
Marette, A. (CRML, Laval University Hospital Research Center, Canada)

Contact Person: Luce Dombrowski (luce.dombrowski@crchul.ulaval.ca)


Glucose transport in skeletal muscle is mainly facilitated by the insulin-responsive GLUT4 glucose transporter. In the basal state, GLUT4 is stored in a transporter-enriched intracellular pool. Following insulin stimulation, GLUT4 is translocated from the intracellular compartment to both the plasma membrane and the T-tubules. We have recently investigated whether the localization of insulin signaling molecules is important for GLUT4 recruitment to the cell surface. We have principally focused on the insulin receptor, IRS-1 and PI3-kinase which are all involved in GLUT4 translocation under insulin stimulation. Subcellular fractionation of unstimulated rat skeletal muscle or L6 cells revealed that the IR is mainly enriched in the plasma membrane fraction whereas IRS-1 and the p85 regulatory subunit of the PI 3-kinase are mostly cytosolic. Insulin (8U/Kg b.w.) stimulation in vivo induced a rapid redistribution of the IR from the cell surface to a GLUT4-enriched intracellular fraction. After 30 minutes, IR was doubled in that fraction and its phosphotyrosine content was also increased more than 5-fold. In vitro autophosphorylation assays confirmed that the redistribution of the IR was paralleled by its activation. In contrast to the IR, the transferrin receptor abundance in the internal fraction was not affected by insulin. IRS-1 content in the IM was not changed by insulin treatment but its phosphorylation in that fraction was augmented 5-fold over basal values. Furthermore, acute (4 min) insulin stimulation increased p85 association with GLUT4-containing intracellular membranes by ~50%. In contrast to the insulin signalling molecules, GLUT4 was rapidly and time-dependently recruited from the intracellular pool reaching maximal depletion after 30 min. These results are consistent with the hypothesis that the coordinated targeting and/or activation of insulin signaling molecules to the GLUT4-containing intracellular membrane pool is a key event in the stimulation of GLUT4 translocation in skeletal muscle.

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Presentation Number SAdombrowski0631
Keywords: glut4, insulin receptor, irs1, p85, translocation

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Dombrowski, L.; Faure, R.; Marette, A.; (1998). Intracellular Traffic of GLUT4 Glucose Trnasporter in Skeletal Muscle. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/klip/dombrowski0631/index.html
© 1998 Author(s) Hold Copyright