Elevation of the number of cell-surface insulin receptors and the rate of 2-deoxyglucose uptake by exposure of 3T3-L1 adipocytes to tolbutamide.
Sulfonylurea compounds are hypoglycemic agents which by unknown mechanisms alter the amount of insulin receptor and the rate of glucose utilization in tissues exposed to the drugs. In this study the effects on insulin binding and uptake of 2-deoxyglucose by 3T3-L1 adipocytes were assessed after maintaining cell monolayers for 1-3 days in medium containing different concentrations of the sulfonylurea, tolbutamide. The amount of 125I-insulin bound by treated monolayers gradually increased to values 150-250% of those of control monolayers after 2-3 days of exposure to 1.5 mM tolbutamide. Such increases in insulin binding capacity arose primarily from an increase in receptor number and not from an alteration in the affinity of the receptor for insulin. Concomitant with the changes observed for the insulin receptor, tolbutamide-treated monolayers expressed 1.5-2-fold higher rates of uptake of 2-deoxyglucose relative to control monolayers at concentrations of insulin between 0 and 10(-10) M. This study thus demonstrates the responsiveness of adipocytes to tolbutamide and also establishes the usefulness of 3T3-L1 cells as a model system in which to study the mechanism of tolbutamide action, both as it relates to the use of sulfonylurea compounds in clinical applications and as possible probes for perturbing and studying relatively uncharacterized regulatory pathways controlling receptor level and biological responses to insulin.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001769:Blood; D002460:Cell Line; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology*
D003837:Deoxy Sugars; D007328:Insulin; D014044:Tolbutamide; D003847:Deoxyglucose; D011972:Receptor, Insulin