PMID- 20804797 OWN - NLM STAT- MEDLINE DCOM- 20110210 LR - 20211203 IS - 1873-5169 (Electronic) IS - 0196-9781 (Print) IS - 0196-9781 (Linking) VI - 31 IP - 12 DP - 2010 Dec TI - Regulation of gastric hormones by systemic rapamycin. PG - 2185-92 LID - 10.1016/j.peptides.2010.08.018 [doi] AB - The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine kinase, is an intracellular fuel sensor critical for cellular energy homeostasis. Gastrointestinal endocrine cells play a vital role in the regulation of energy balance by secreting hormones that inform the brain about energy supply. Here we showed the localization of mTOR signaling molecules in more than 90% of gastric ghrelin cells and 36+/-3% of gastrin cells, while no somatostatin-positive cell showed phospho-S6K1 immunoreactivity. Inhibition of mTOR significantly stimulated expression of gastric ghrelin mRNA and protein, and the concentration of plasma ghrelin (2.06+/-0.34 ng/ml vs. 12.53+/-3.9 ng/ml, p<0.05), inhibited gastrin synthesis and secretion (75.01+/-6.71 pg/ml vs. 54.04+/-3.65 pg/ml, p<0.05), but had no effect on somatostatin production (165.2+/-25.07 pg/ml vs. 178.9+/-29.14 pg/ml, p=0.73). Gastric mTOR is a gastric sensor whose activity is linked to the differential regulation of gastric hormone production and release. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Xu, Geyang AU - Xu G AD - Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China. FAU - Li, Yin AU - Li Y FAU - An, Wenjiao AU - An W FAU - Zhao, Jing AU - Zhao J FAU - Xiang, Xinxin AU - Xiang X FAU - Ding, Li AU - Ding L FAU - Li, Ziru AU - Li Z FAU - Guan, Youfei AU - Guan Y FAU - Wang, Xian AU - Wang X FAU - Tang, Chaoshu AU - Tang C FAU - Zhu, Yi AU - Zhu Y FAU - Wang, Nanping AU - Wang N 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 - R37 DK043225/DK/NIDDK NIH HHS/United States GR - R01DK043225/DK/NIDDK NIH HHS/United States GR - R01 DK054032/DK/NIDDK NIH HHS/United States GR - R01 DK043225-13/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 - 20100908 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Gastrins) RN - 0 (Ghrelin) RN - 51110-01-1 (Somatostatin) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Blotting, Western MH - Enteroendocrine Cells/drug effects/metabolism MH - Gastrins/*blood/genetics/metabolism MH - Ghrelin/*blood/genetics/metabolism MH - Humans MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Polymerase Chain Reaction MH - Rats MH - Sirolimus/*pharmacology MH - Somatostatin/*blood/genetics/metabolism MH - TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC2995266 MID - NIHMS232852 EDAT- 2010/09/02 06:00 MHDA- 2011/02/11 06:00 PMCR- 2011/12/01 CRDT- 2010/09/01 06:00 PHST- 2010/06/18 00:00 [received] PHST- 2010/08/20 00:00 [revised] PHST- 2010/08/20 00:00 [accepted] PHST- 2010/09/01 06:00 [entrez] PHST- 2010/09/02 06:00 [pubmed] PHST- 2011/02/11 06:00 [medline] PHST- 2011/12/01 00:00 [pmc-release] AID - S0196-9781(10)00358-X [pii] AID - 10.1016/j.peptides.2010.08.018 [doi] PST - ppublish SO - Peptides. 2010 Dec;31(12):2185-92. doi: 10.1016/j.peptides.2010.08.018. Epub 2010 Sep 8.