Interactions between effects of W-7, insulin, and hypoxia on glucose transport in skeletal muscle.
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)
Youn
J H
JH
Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033.
Gulve
E A
EA
Henriksen
E J
EJ
Holloszy
J O
JO
D019325:3-O-Methylglucose; D000585:Aminacrine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003620:Dantrolene / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology
D007328:Insulin; D008757:Methylglucosides; D013449:Sulfonamides; D014665:Vasodilator Agents; D014316:Tritium; D019325:3-O-Methylglucose; C017967:W 7; D000585:Aminacrine; D003620:Dantrolene; D005947:Glucose