Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells

Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone secreted by intestinal L cells and vital for postprandial glycemic control. As open-type enteroendocrine cells, whether L cells can sense mechanical stimuli caused by chyme and thus regulate GLP-1 synthesis and secretion is unexplored. Molecul...

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Main Authors: Yanling Huang, Haocong Mo, Jie Yang, Luyang Gao, Tian Tao, Qing Shu, Wenying Guo, Yawen Zhao, Jingya Lyu, Qimeng Wang, Jinghui Guo, Hening Zhai, Linyan Zhu, Hui Chen, Geyang Xu
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-11-01
Series:eLife
Subjects:
Piezo1
glucagon-like peptide 1
intestinal L cells
CaMKKβ
CaMKIV
mechanistic target of rapamycin
Online Access:https://elifesciences.org/articles/97854
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Summary:Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone secreted by intestinal L cells and vital for postprandial glycemic control. As open-type enteroendocrine cells, whether L cells can sense mechanical stimuli caused by chyme and thus regulate GLP-1 synthesis and secretion is unexplored. Molecular biology techniques revealed the expression of Piezo1 in intestinal L cells. Its level varied in different energy status and correlates with blood glucose and GLP-1 levels. Mice with L cell-specific loss of Piezo1 (Piezo1 IntL-CKO) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKKβ/CaMKIV-mTORC1 signaling pathway under normal chow diet or high-fat diet. Activation of the intestinal Piezo1 by its agonist Yoda1 or intestinal bead implantation increased the synthesis and secretion of GLP-1, thus alleviated glucose intolerance in diet-induced-diabetic mice. Overexpression of Piezo1, Yoda1 treatment or stretching stimulated GLP-1 production and CaMKKβ/CaMKIV-mTORC1 signaling pathway, which could be abolished by knockdown or blockage of Piezo1 in primary cultured mouse L cells and STC-1 cells. These experimental results suggest a previously unknown regulatory mechanism for GLP-1 production in L cells, which could offer new insights into diabetes treatments.
ISSN:2050-084X

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