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Am J Physiol Regul Integr Comp Physiol 267: R888-R894, 1994;
0363-6119/94 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 4 888-R894, Copyright © 1994 by American Physiological Society

ARTICLES

Interactions between effects of W-7, insulin, and hypoxia on glucose transport in skeletal muscle

J. H. Youn, E. A. Gulve, E. J. Henriksen and J. O. Holloszy
Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033.

The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) stimulates glucose transport in skeletal muscle, apparently by raising cytosolic Ca2+ (P. Palade. J. Biol. Chem. 262: 6142-6148, 1987; J.H. Youn, E.A. Gulve, and J.O. Holloszy. Am. J. Physiol. 260 (Cell Physiol. 29): C555-C561, 1991). This study was performed to describe the interactions between the effects of W-7 and those of hypoxia and of insulin on glucose transport. The effect on 3-O-methylglucose (3-MG) transport of 50 microM W-7 was additive to the effect of a maximal insulin stimulus (2,000 microU/ml) but not to the effect of maximal (60 min) hypoxic stimulus, suggesting that W-7 stimulates glucose transport via the same pathway as hypoxia, independent of the pathway activated by insulin. The effect of 50 microM W-7 was additive to that of a submaximal (20 min) hypoxia stimulus, indicating that W-7 does not interfere with the stimulation of glucose transport by hypoxia. In contrast, 50 microM W-7 had an inhibitory effect on stimulation of 3-MG transport by submaximally effective insulin levels, causing a fivefold increase in the concentration of insulin needed to produce a half-maximal stimulation of 3-MG transport, from approximately 70 to approximately 350 microU/ml (P < 0.05). Thus these data demonstrate that W-7 selectively inhibits insulin stimulation of glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)


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