Metabolic effects of glibenclamide in isolated rat hepatocytes in the absence of extracellular Ca2+.
We examined the metabolic effects of glibenclamide, a potent second-generation sulfonylurea, in isolated rat hepatocytes incubated in the absence of extracellular Ca2+. We first demonstrated in the present study that glibenclamide caused a significant increase in basal glucose release and lactate production without any modification of intracellular Ca2+ concentration or cAMP levels in isolated rat hepatocytes. Furthermore, glibenclamide inhibited the noradrenaline-induced increase in cAMP accumulation, while activation of glycogenolysis by noradrenaline was not suppressed by this agent. Our data indicate that glibenclamide exerts its metabolic effects independent of intracellular Ca2+ mobilization and cAMP accumulation.
Nomura
T
T
Department of Pharmacology, Fujita Health University School of Medicine, Aichi, Japan.
Ohtsuki
M
M
Watanabe
T
T
Hasegawa
S
S
Matsui
S
S
Tomita
A
A
Sumi-Ichinose
C
C
Nomura
H
H
Hagino
Y
Y
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000242:Cyclic AMP; D005905:Glyburide; D002118:Calcium