Role of calcium and cyclic adenosine 3',5'-monophosphate in the antilipolytic effect of tolbutamide and glibenclamide.

Abstract

Tolbutamide (1 mM) and glibenclamide (0.1 mM) reduced lipolysis due to adrenaline, noradrenaline, isoprenaline, glucagon, and ACTH, whereas theophylline-induced glycerol production was only marginally affected. Furthermore, the effect of dibutyryl cyclic AMP on lipolysis was markedly decreased by low concentrations of both drugs. The antilipolytic action of glibenclamide and, to a smaller degree, of tolbutamide was highly dependent on the calcium concentration in the incubation medium used after preparation of fat cells in the absence of calcium. In the presence of isoprenaline as a lipolytic agent the antilipolytic effect of glibenclamide was progressively enhanced by raising the calcium concentration up to 1.2 mM. Howver, further elevation of calcium to 2.4 mM resulted in a loss of antilipolytic effect. Basal cyclic AMP levels of isolated fat cells were increased twofold by glibenclamide or tolbutamide. In contrast to the effect of glibenclamide, cyclic AMP levels in the presence of isoprenaline were further increased by tolbutamide. Low Km cyclic AMP phosphodiesterase of fat cells was inhibited by tolbutamide as well as by glibenclamide. The results indicate that the antilipolytic action of sulfonylurea drugs is closely related to changes in calcium metabolism but independent of cyclic AMP levels.