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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shibata, Hiroshi Kojima, Itaru Ma, Jinhui Nakagawa, Yuko |
| Description | Author Affiliation: Ma J ( From the Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.) |
| Abstract | Although insulin acutely stimulates glucose uptake by promotion of GLUT4 translocation from intracellular compartments to the plasma membrane in adipocytes and muscles, long term insulin stimulation causes GLUT4 depletion that is particularly prominent in the insulin-responsive GLUT4 storage compartment. This effect is caused mainly by accelerated lysosomal degradation of GLUT4, although the mechanism is not fully defined. Here we show that insulin acutely induced dissociation of retromer components from the low density microsomal membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on the activity of protein kinase CK2 but not phosphatidylinositol 3-kinase or extracellular signal-regulated kinase 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif (Vps35-S7A) was resistant to insulin-induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Furthermore, insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 1 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-01-03 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adipocytes Metabolism Casein Kinase II Down-Regulation Physiology Glucose Transporter Type 4 Insulin Oxidative Stress 3T3 Cells Adaptor Proteins, Vesicular Transport Genetics Cytology Animals Drug Effects Gene Knockdown Techniques Hypoglycemic Agents Pharmacology Intracellular Membranes Liposomes Mice Microsomes Mitogen-Activated Protein Kinase 3 Phosphatidylinositol 3-Kinases Phosphorylation Protein Transport Proteolysis Vesicular Transport Proteins Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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