Format

Send to

Choose Destination
Mol Cell Endocrinol. 2015 Nov 15;416:9-18. doi: 10.1016/j.mce.2015.08.016. Epub 2015 Aug 13.

Ghrelin regulates GLP-1 production through mTOR signaling in L cells.

Author information

1
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China. Electronic address: xugeyangliang@163.com.
2
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong, 510632, China.
3
Shenzhen University Diabetes Center, Shenzhen University Health Science Center, 3688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong, 518060, China.
4
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA.
5
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.

Abstract

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.

KEYWORDS:

Enteroendocrine L cells; GHSR1a; GLP-1; Ghrelin; Incretin; mTORC1

PMID:
26279396
DOI:
10.1016/j.mce.2015.08.016
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center