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

First Author  Xu G Year  2015
Journal  Mol Cell Endocrinol Volume  416
Pages  9-18 PubMed ID  26279396
Mgi Jnum  J:229176 Mgi Id  MGI:5751010
Doi  10.1016/j.mce.2015.08.016 Citation  Xu G, et al. (2015) Ghrelin regulates GLP-1 production through mTOR signaling in L cells. Mol Cell Endocrinol 416:9-18
abstractText  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.
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