Characterization of the sulfonylurea-induced potentiation of the insulin response in cultured 3T3 adipocytes.
Studies were carried out to determine the role of sulfonylureas in the regulation of insulin-sensitive hexose uptake in cultured 3T3 adipocytes. Exposure (0-72 hr) of cells to the sulfonylurea-derivative tolbutamide (0.05-0.3 mg/ml) induced a time- and concentration-dependent potentiation of the stimulatory effect of insulin on hexose uptake (500 vs 340%). The effect was maximal within 24 hr and completely reversible. It was strictly limited to the presence of insulin. Basal hexose uptake and insulin binding were not affected by the drug. High concentrations of the agent (greater than 0.3 mg/ml) induced a decrease in insulin response, suggesting a concentration optimum. Lineweaver-Burk analysis of uptake data revealed that the potentiating effect of tolbutamide was due to enhancement of the insulin-induced increase in apparent Vmax, i.e. in the number or activity of hexose transporters. This enhancement was inhibited by cycloheximide (1 microgram/ml), indicating involvement of protein synthesis in the induction of the effect. It is concluded that sulfonylureas act by influencing synthesis of protein(s) which potentiate the effect of insulin on hexose uptake.
D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006601:Hexoses / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology*
D006601:Hexoses; D007328:Insulin; D014044:Tolbutamide