AJP - Endocrinology and Metabolism, Vol 267, Issue 1 E14-E23, Copyright © 1994 by American Physiological Society

ARTICLES

Phenylarsine oxide inhibits insulin-stimulated protein phosphatase 1 activity and GLUT-4 translocation

N. Begum
Diabetes Research Laboratory, Winthrop University Hospital, Mineola 11501.

Phenylarsine oxide (PAO) has previously been shown to inhibit insulin-stimulated glucose transport without affecting insulin binding and tyrosine kinase activity of insulin receptor (S. C. Frost and M. D. Lane. J. Biol. Chem. 260: 2646-2652, 1985). This study examines the effect of PAO on insulin's ability to activate adipocyte protein phosphatase 1 (PP-1) and dephosphorylate GLUT-4, the insulin-sensitive glucose transporter. In particulate fractions, insulin stimulated PP-1 activity (40% increase over basal with phosphorylase a) in a time- and dose-dependent manner (half-maximal effect of 0.89 nM in 1 min). Insulin did not alter cytosolic PP-1 activity. With GLUT-4 as a substrate, insulin caused more than twofold stimulation of particulate PP-1 activity. Addition of PAO (5 microM) before or after insulin treatment abolished insulin's effect on PP-1 activation. The presence of 2,3-dimercaptopropanol (200 microM) prevented the effect of PAO on PP-1 activation and glucose uptake. In addition, PAO significantly increased GLUT-4 phosphorylation, blocked insulin-stimulated dephosphorylation, and partially diminished insulin-stimulated translocation of GLUT-4. We conclude that PAO may interfere with the components of insulin signal transduction pathways that lead to the activation of PP-1 and this may be responsible for the observed inhibition in insulin action.

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