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ACUTE REGULATION OF GLUT1 FUNCTION: THE ROLE OF DETERGENT-RESISTANT MEMBRANE DOMAINS
| Title: | ACUTE REGULATION OF GLUT1 FUNCTION: THE ROLE OF DETERGENT-RESISTANT MEMBRANE DOMAINS |
| Author: | Rubin, Darrell |
| Description: | Identifying which processes and proteins control glucose transport could provide important clues to understanding and treating a number of clinical entities including diabetes and some cancers. Glucose transport across the plasma membrane occurs by either sodium-dependent or independent glucose transporters. In order to study the mechanisms which control acute changes in glucose transport by sodium-independent glucose transporters, we use the non-transformed rat liver – derived Clone 9 cell line. These cells respond to the acute inhibition of oxidative phosphorylation by azide with a 4-6 fold stimulation of glucose transport and a 1.8 fold increase in the amount of glucose transporter 1 (Glut1) in the plasma membrane. In Clone 9 cells under basal conditions, ~38 % of Glut1 in the post-nuclear lysate is localized to the detergent-resistant membrane (DRM) microdomains. Acute exposure to azide decreased this figure by ~40 %. In order to examine the effects of azide on Glut1 localization to the plasma membrane of the Clone 9 cell, we performed subcellular fractionation of the post-nuclear homogenates. Approximately 30 % of the Glut1 in the post-nuclear homogenate was recovered in the plasma membrane (PM) compartment and 50 % of this PM Glut1 localized to the DRM fraction. Acute inhibition of oxidative phosphorylation with azide resulted in a 1.6-fold increase in the total abundance of Glut1 in the PM and was associated with a 2.9 fold increase in the abundance of Glut1 in the non-DRM fraction but no significant change in the content of Glut1 in the DRM fraction. We conclude that in the Clone 9 cell Glut1 localizes to detergent-resistant membrane microdomains in the plasma membrane. Moreover, in these cells the azide – induced increase in glucose transport is associated with an increase of Glut1 abundance in the non – DRM fraction of the plasma membrane and a decrease of Glut1 association with the DRM fraction of a membrane compartment other than the plasma membrane. These findings indicate that the distribution of Glut1 to the DRM and non-DRM domains of the cellular membrane compartments contribute, in part, to the mechanisms of glucose transport regulation in response to the acute inhibition of oxidative phosphorylation. |
| Permanent Link: |
http://rave.ohiolink.edu/etdc/view?acc_num=case1087996732
http://hdl.handle.net/2374.OX/16191 |
| Date: | 2004 |
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