Enhanced lipolysis in 3T3-L1 adipocytes following prolonged exposure to tolbutamide.

The effect of tolbutamide on lipolysis was examined in 3T3-L1 adipocytes. Whereas lipolysis was reversibly inhibited by tolbutamide, prolonged treatment with this agent dose-dependently increased both basal and isoproterenol-stimulated lipolysis in washed adipocytes. The latter effect of tolbutamide was not accompanied with altered cAMP levels in the cells and was abolished in the presence of cycloheximide. Moreover, the lipolytic responses induced by isobutylmethylxanthine, forskolin and dibutyryl cAMP were also augmented by prolonged treatment of adipocytes with tolbutamide. Thus, it appears that development of enhanced lipolysis in 3T3-L1 adipocytes following prolonged exposure to tolbutamide requires continuous protein synthesis and probably involves a step distal to cAMP production.