Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle.
The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (greater than 5 microM) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3-MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (greater than or equal to 20 microM) prevented approximately 80% of the increase in 3-MG transport caused by insulin, it resulted in only a approximately 50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 microM) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
E J
EJ
Henriksen
J O
JO
Holloszy
D019325:3-O-Methylglucose; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D001152:Arsenicals; D007328:Insulin; D008757:Methylglucosides; D008759:Methylglycosides; C029341:oxophenylarsine; D019325:3-O-Methylglucose; D014638:Vanadates; D006861:Hydrogen Peroxide; D010738:Type C Phospholipases