PMID- 21063108 OWN - NLM STAT- MEDLINE DCOM- 20110302 LR - 20220318 IS - 1421-9778 (Electronic) IS - 1015-8987 (Print) IS - 1015-8987 (Linking) VI - 26 IP - 4-5 DP - 2010 TI - Modulation of ghrelin O-acyltransferase expression in pancreatic islets. PG - 707-16 LID - 10.1159/000322338 [doi] AB - 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. CONCLUSION: 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. CI - Copyright (c) 2010 S. Karger AG, Basel. FAU - An, Wenjiao AU - An W AD - Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China. FAU - Li, Yin AU - Li Y FAU - Xu, Geyang AU - Xu G FAU - Zhao, Jing AU - Zhao J FAU - Xiang, Xinxin AU - Xiang X FAU - Ding, Li AU - Ding L FAU - Li, Jing AU - Li J FAU - Guan, Youfei AU - Guan Y FAU - Wang, Xian AU - Wang X FAU - Tang, Chaosu AU - Tang C FAU - Li, Xiaoying AU - Li X FAU - Mulholland, Michael AU - Mulholland M FAU - Zhang, Weizhen AU - Zhang W LA - eng GR - R01 DK043225/DK/NIDDK NIH HHS/United States GR - R01 DK054032/DK/NIDDK NIH HHS/United States GR - R37 DK043225/DK/NIDDK NIH HHS/United States GR - R01DK043225/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20101029 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Anti-Bacterial Agents) RN - 0 (Insulin) RN - 0 (Tsc1 protein, mouse) RN - 0 (Tsc1 protein, rat) RN - 0 (Tuberous Sclerosis Complex 1 Protein) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.3.- (Acyltransferases) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.- (ghrelin O-acyltransferase, rat) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Acyltransferases/genetics/*metabolism MH - Animals MH - Anti-Bacterial Agents/pharmacology MH - Insulin/pharmacology MH - Islets of Langerhans/*enzymology MH - Male MH - Mice MH - Promoter Regions, Genetic MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/metabolism MH - Tuberous Sclerosis Complex 1 Protein MH - Tumor Suppressor Proteins/metabolism PMC - PMC3048940 EDAT- 2010/11/11 06:00 MHDA- 2011/03/03 06:00 PMCR- 2011/10/01 CRDT- 2010/11/11 06:00 PHST- 2010/08/25 00:00 [accepted] PHST- 2010/11/11 06:00 [entrez] PHST- 2010/11/11 06:00 [pubmed] PHST- 2011/03/03 06:00 [medline] PHST- 2011/10/01 00:00 [pmc-release] AID - 000322338 [pii] AID - cpb0026-0707 [pii] AID - 10.1159/000322338 [doi] PST - ppublish SO - Cell Physiol Biochem. 2010;26(4-5):707-16. doi: 10.1159/000322338. Epub 2010 Oct 29.