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Inverse relationship between GLUT-4 phosphorylation and its intrinsic activity
J E Reusch1, K E Sussman, B Draznin
1Department of Medicine, Veterans Affairs Medical Center, Denver, Colorado 80220.
The Journal of Biological Chemistry
|February 15, 1993
Summary
Parathyroid hormone (PTH) increases glucose transporter 4 (GLUT-4) phosphorylation in rat adipocytes, impairing its intrinsic activity. This phosphorylation hinders insulin
Area of Science:
- Molecular Biology
- Cellular Metabolism
- Endocrinology
Background:
- Glucose transporter 4 (GLUT-4) is crucial for insulin-stimulated glucose uptake in adipocytes.
- Regulation of GLUT-4 function by post-translational modifications like phosphorylation is key to metabolic control.
Purpose of the Study:
- To investigate the impact of parathyroid hormone (PTH)-induced phosphorylation on GLUT-4 function in isolated rat adipocytes.
- To determine if GLUT-4 phosphorylation affects its intrinsic activity and response to insulin.
Main Methods:
- Adipocytes were labeled with 32P and treated with PTH and insulin.
- GLUT-4 phosphorylation was assessed via immunoprecipitation, autoradiography, and densitometry.
- GLUT-4 intrinsic activity was measured using [14C]2-deoxyglucose uptake in plasma membrane vesicles.
Main Results:
- PTH significantly increased GLUT-4 phosphorylation and blocked insulin-induced dephosphorylation.
- Phosphorylated GLUT-4 exhibited significantly reduced intrinsic activity.
- Calcium channel blockers and cyclic AMP antagonists restored GLUT-4 intrinsic activity in PTH-treated cells.
Conclusions:
- GLUT-4 phosphorylation, induced by PTH, significantly impairs its intrinsic activity.
- Phosphorylation of GLUT-4 interferes with insulin's ability to stimulate glucose transport.
- These findings highlight a novel regulatory mechanism of glucose uptake potentially relevant to metabolic disorders.