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

Abstract

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)

• Authors: J H Youn, E A Gulve, E J Henriksen, J O Holloszy
• Journal: The American journal of physiology (Am J Physiol) Vol. 267 Issue 4 Pt 2 Pg. R888-94 (Oct 1994) ISSN: 0002-9513 [Print] United States
• PMID: 7943429 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Insulin
• Methylglucosides
• Sulfonamides
• Vasodilator Agents
• Tritium
• 3-O-Methylglucose
• W 7
• Aminacrine
• Dantrolene
• Glucose

Topics

• 3-O-Methylglucose
• Aminacrine (pharmacology)
• Animals
• Biological Transport (drug effects)
• Dantrolene (pharmacology)
• Glucose (metabolism)
• Hypoxia
• In Vitro Techniques
• Insulin (pharmacology)
• Kinetics
• Male
• Methylglucosides (metabolism)
• Muscles (drug effects, metabolism)
• Rats
• Rats, Wistar
• Sulfonamides (pharmacology)
• Tritium
• Vasodilator Agents (pharmacology)