Regulation of gastric hormones by systemic rapamycin.
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.
Xu
Geyang
G
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
Li
Yin
Y
An
Wenjiao
W
Zhao
Jing
J
Xiang
Xinxin
X
Ding
Li
L
Li
Ziru
Z
Guan
Youfei
Y
Wang
Xian
X
Tang
Chaoshu
C
Zhu
Yi
Y
Wang
Nanping
N
Li
Xiaoying
X
Mulholland
Michael
M
Zhang
Weizhen
W
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
D005755:Gastrins; D054439:Ghrelin; D013004:Somatostatin; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
Am J Pathol. 1984 Jun;115(3):458-68
6375394
J Clin Endocrinol Metab. 2002 Jan;87(1):240-4
11788653
Clin Endocrinol (Oxf). 2002 Feb;56(2):203-6
11874411
J Clin Endocrinol Metab. 2003 Jan;88(1):174-8
12519848
Psychol Rev. 1975 May;82(3):200-24
168602
Microsc Res Tech. 2000 Mar 1;48(5):272-81
10700044
Eur J Biochem. 2002 Nov;269(22):5338-49
12423332
Acta Physiol Scand. 1976 Jan;96(1):19-28
1251745
Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G7-13
14665437
J Physiol. 1906 Mar 13;34(1-2):133-44
16992839
Science. 2006 May 12;312(5775):927-30
16690869
Gastroenterology. 2007 May;132(6):2158-68
17498509
J Cell Sci. 2009 Oct 15;122(Pt 20):3589-94
19812304
Eur J Biochem. 2000 Nov;267(21):6321-30
11029573
N Engl J Med. 1986 May 1;314(18):1145-51
3007986
Nature. 2004 Sep 9;431(7005):200-5
15306821
Cell Metab. 2009 Apr;9(4):362-74
19356717
Digestion. 1975;13(1-2):15-26
1201817
Biochem Biophys Res Commun. 1973 Jan 4;50(1):127-33
4734245
Annu Rev Physiol. 1997;59:243-56
9074763
Diabetes Res Clin Pract. 2008 Nov 13;82 Suppl 1:S59-62
18926585
Am J Surg Pathol. 2001 Oct;25(10):1261-7
11688460
Physiol Res. 2003;52(1):61-6
12625808
Physiol Rev. 2005 Apr;85(2):495-522
15788704
Diabetes. 2001 Aug;50(8):1714-9
11473029
Endocrinology. 2009 Aug;150(8):3637-44
19406939
Int J Biol Markers. 1999 Jul-Sep;14(3):160-6
10569138
Nat Genet. 2005 Jan;37(1):19-24
15624019
J Clin Invest. 2007 Jan;117(1):13-23
17200702
Regul Pept. 2000 Sep 25;93(1-3):31-5
11033050
Science. 2001 Nov 2;294(5544):1102-5
11691993
Acta Biochim Biophys Sin (Shanghai). 2008 Oct;40(10):841-7
18850048
Cancer. 1999 Sep 1;86(5):858-65
10463986
Endocrinology. 2005 Mar;146(3):1473-81
15604215