Inhibitory effects of diazoxide or polymyxin B on glucose transport by isolated rat erythrocytes or adipocytes.
The inhibitory effects of diazoxide or polymyxin B on 3-O-methylglucose uptake were studied in isolated rat erythrocytes or adipocytes to elucidate the mechanisms of the actions of these agents. One to three mmol/L diazoxide significantly inhibited 3-O-methylglucose uptake into erythrocytes by 11-33% without altering the equilibrium space, while 0.3 mmol/L diazoxide did not. The inhibitory effect was exerted in a dose-dependent manner in this concentration range. To test whether polymyxin B affects the process of insulin action or the glucose transport activity recruited by insulin, adipocytes prestimulated with insulin and exposed to 2 mmol/L potassium cyanide (KCN) were employed since the cells, on which glucose transporters recruited by insulin were located quiescently, were useful to estimate the effect of an agent on glucose transport activity per se. Polymyxin B (100 micrograms/mL) inhibited the insulin-stimulated uptake activity in this transport system by 22.5% while it inhibited the insulin-stimulated uptake activity in intact adipocytes which were not exposed to KCN by 32.2%. These results suggest that diazoxide inhibits the function of the erythrocyte glucose transporter, GLUT1 (classified by Bell et al.), and indicate that the inhibition of the glucose transport activity recruited by insulin is the major effect of polymyxin B (100 micrograms/mL) and the inhibition of the process of insulin action is rather small.
Goto
Y
Y
Department of Pediatrics, Ehime University School of Medicine, Japan.
Kida
K
K
Kaino
Y
Y
Ito
T
T
Matsuda
H
H
D019325:3-O-Methylglucose; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D046508:Culture Techniques; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008757:Methylglucosides / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D011112:Polymyxin B / Q000494:pharmacology*; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D011112:Polymyxin B; D011190:Potassium Cyanide; D003981:Diazoxide