Modulation of ghrelin O-acyltransferase expression in pancreatic islets.
BACKGROUND
Ghrelin, the only identified circulating orexigenic signal, is unique in structure in which a specific acyl-modification of its third serine occurs. This acylation is necessary for ghrelin to bind to its receptor and to exert its biologic activity, which is catalyzed by ghrelin O-acyltransferase (GOAT). Although ghrelin is mainly secreted from gastric X/A like endocrine cells, it is also expressed in pancreatic islet cells and regulates insulin secretion. In this study, we examined the expression and regulation of GOAT in pancreas.


METHODS
GOAT mRNA and immunoreactivity were examined in pancreatic islets and INS-1 cells by RT-PCR and immunofluorescent staining or Western blotting.


RESULTS
Insulin inhibits the expression of GOAT mRNA and GOAT promoter activity in a dose and time-dependent manner. The mammalian target of rapamycin (mTOR) is activated by insulin. Blocking mTOR signaling by either rapamycin or overexpression of its negative regulator tuberous sclerosis complex 1 (TSC1) or TSC2 attenuates the inhibitory effect of insulin on the transcription and translation of GOAT.


CONCLUSIONS
Our study suggests that GOAT is present in pancreatic islet cells and that insulin inhibits the expression of GOAT via the mediation of mTOR signaling.
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Wenjiao
W
An
Yin
Y
Li
Geyang
G
Xu
Jing
J
Zhao
Xinxin
X
Xiang
Li
L
Ding
Jing
J
Li
Youfei
Y
Guan
Xian
X
Wang
Chaosu
C
Tang
Xiaoying
X
Li
Michael
M
Mulholland
Weizhen
W
Zhang
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000201:enzymology*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007328:Insulin; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000217:Acyltransferases; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C534462:ghrelin O-acyltransferase, rat; D020123:Sirolimus