Ghrelin regulates GLP-1 production through mTOR signaling in L cells.
Glucagon-like peptide (GLP-1), an intestinal incretin produced in L-cells and released in response to meal intake, functions to promote insulin secretion and to decrease plasma glucose. Ghrelin is an orexigenic hormone critical for glucose homeostasis. The molecular mechanism by which ghrelin alters GLP-1 production remains largely unknown. Here we showed that ghrelin attenuates GLP-1 production through mTOR signaling. In GHSR1a null mice, ileal mTOR signaling, proglucagon and circulating GLP-1 were significantly increased. Antagonism of the GHSR1a by D-Lys-3-GHRP-6 increased GLP-1 synthesis and release in STC-1 cells. Treatment of STC-1 cells with ghrelin decreased the production of GLP-1. This effect was associated with a significant inhibition of mTOR signaling. Overexpression of ghrelin inhibited proglucagon promoter activity and GLP-1 production. Inhibition of mTOR activity by mTOR siRNA blocked D-Lys-3-GHRP-6 induced GLP-1 production in STC-1 cells. Our results suggest that mTOR signaling mediates the inhibitory effect of ghrelin on GLP-1 production.
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China. Electronic address: xugeyangliang@163.com.
Geyang
G
Xu
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
Xiaosi
X
Hong
Shenzhen University Diabetes Center, Shenzhen University Health Science Center, 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong, 518060, China.
Hong
H
Tang
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
Sushi
S
Jiang
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
Fenting
F
Liu
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
Zhemin
Z
Shen
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA.
Ziru
Z
Li
Shenzhen University Diabetes Center, Shenzhen University Health Science Center, 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong, 518060, China; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA. Electronic address: weizhenz@umich.edu.
Weizhen
W
Zhang
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D045744:Cell Line, Tumor; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D001786:Blood Glucose; D054439:Ghrelin; D054795:Incretins; D007328:Insulin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D052216:Glucagon-Like Peptide 1; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
Enteroendocrine L cells; GHSR1a; GLP-1; Ghrelin; Incretin; mTORC1