Inhibitory effect of obestatin on glucose-induced insulin secretion in rats.
Obestatin is a bioactive peptide encoded by the same gene that encodes ghrelin. Our aim was to investigate the effect of obestatin on insulin secretion. We evaluated the effects of obestatin on insulin secretion from rat islet cells which had been incubated overnight in the presence of 8.3, 11.1, and 22.2 mmol/l of glucose. In vivo, the serum levels of glucose and insulin were measured 0, 1, 5, 10, 20, 40, and 60 min after the intravenous administration of saline or glucose (1g/kg), with or without obestatin, and the area under the 60 min curve of insulin concentration (AUC(insulin)) was calculated. Obestatin (0.01-100 nmol/l) inhibited insulin secretion from rat islets in a dose-dependent fashion. In vivo, when administered intravenously to rats together with glucose, obestatin (10, 50, and 250 nmol/kg) inhibited both the rapid 1-min insulin response and the AUC(insulin) in a dose-dependent fashion. Our data demonstrate that under glucose-stimulated conditions, exogenous obestatin acts as a potent inhibitor of insulin secretion in anaesthetized rats in vivo as well as in cultured islets in vitro.
Ren
An-Jing
AJ
The Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Guo
Zhi-Fu
ZF
Wang
Yang-Kai
YK
Wang
Li-Gang
LG
Wang
Wei-Zhong
WZ
Lin
Li
L
Zheng
Xing
X
Yuan
Wen-Jun
WJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D007329:Insulin Antagonists; D005947:Glucose