Endocrine

, Volume 10, Issue 1, pp 13–18

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle

Authors

  • André Marette
    • Department of Physiology and Lipid Research UnitLaval University Hospital Research Centre (CHUL)
  • Dimitrios Dimitrakoudis
    • Department of Physiology, Faculty of MedicineUniversity of Toronto
    • Department of Programme in Cell BiologyThe Hospital for Sick Children
  • Qing Shi
    • Department of Physiology, Faculty of MedicineUniversity of Toronto
  • Carol D. Rodgers
    • Department of Physiology, Faculty of MedicineUniversity of Toronto
  • Amira Klip
    • Department of Programme in Cell BiologyThe Hospital for Sick Children
  • Mladen Vranic
    • Department of Medicine, Faculty of MedicineUniversity of Toronto
Article

DOI: 10.1385/ENDO:10:1:13

Cite this article as:
Marette, A., Dimitrakoudis, D., Shi, Q. et al. Endocr (1999) 10: 13. doi:10.1385/ENDO:10:1:13

Abstract

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341–348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state:
  1. 1.

    Control rats.

     
  2. 2.

    Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels.

     
  3. 3.

    STZ-diabetic rats made normoglycemic with phlorizin treatment.

     
  4. 4.

    Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min.

     

The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced down-regulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.

Key Words

Glucose transporter GLUT1 phlorizin glycemia streptozotocin

Copyright information

© Humana Press Inc. 1999