W-7 specifically inhibits insulin-induced increase in glucose transport.
To elucidate the role of calmodulin in insulin action, we examined the effect of the calmodulin antagonists, W-7 and W-5, on glucose transport in isolated rat adipocytes. W-7 inhibited insulin-stimulated 2-deoxyglucose uptake by 18% at 100 microM, but it did not affect basal uptake levels. W-5, a less potent analogue of W-7, however, had no significant effect at the same concentration, indicating that the effect was specific to calmodulin. Similar results were observed in a 3-O-methylglucose uptake study. Kinetic analysis of 2-deoxyglucose uptake revealed that W-7 affected the insulin-induced increase in Vmax but not Km. These results suggest that calmodulin modifies insulin action in the glucose transport system.
Ishibashi
O
O
Third Department of Medicine, Shiga University of Medical Science, Ohtsu, Japan.
Kobayashi
M
M
Sasaoka
T
T
Sugibayashi
M
M
Shigeta
Y
Y
D019325:3-O-Methylglucose; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D003847:Deoxyglucose / Q000378:metabolism / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D007328:Insulin; D008757:Methylglucosides; D013449:Sulfonamides; D019325:3-O-Methylglucose; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D003847:Deoxyglucose; D011972:Receptor, Insulin; D005947:Glucose