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

Autor:	Huang Y; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Mo H; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Yang J; Department of Pathology, School of Basic Medicine, Guangzhou Medical University, Guangdong, China., Gao L; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Tao T; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Shu Q; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Guo W; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Zhao Y; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Lyu J; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China., Wang Q; Biotherapy Center, Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China., Guo J; School of Medicine, The Chinese University of Hong Kong, Shenzhen, China., Zhai H; Endoscopy Center, The First Affiliated Hospital of Jinan University, Guangzhou, China., Zhu L; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China., Chen H; Biotherapy Center, Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China., Xu G; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou, China.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Nov 07; Vol. 13. Date of Electronic Publication: 2024 Nov 07.
DOI:	10.7554/eLife.97854
Abstrakt:	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. Competing Interests: YH, HM, JY, LG, TT, QS, WG, YZ, JL, QW, JG, HZ, LZ, HC, GX No competing interests declared (© 2024, Huang, Mo, Yang et al.)
Databáze:	MEDLINE
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