title: Regulation of gastric hormones by systemic rapamycin.
abstract: 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.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Geyang
authors.initials: G
authors.lastname: Xu
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Wenjiao
authors.initials: W
authors.lastname: An
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xinxin
authors.initials: X
authors.lastname: Xiang
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Ziru
authors.initials: Z
authors.lastname: Li
authors.forename: Youfei
authors.initials: Y
authors.lastname: Guan
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Mulholland
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D054439:Ghrelin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D013004:Somatostatin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005755:Gastrins; D054439:Ghrelin; D013004:Somatostatin; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
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