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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 (\n                    <jats:italic>Piezo1<\/jats:italic>\n                    IntL-CKO) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKK\u03b2\/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 CaMKK\u03b2\/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.\n                  <\/jats:p>","DOI":"10.7554\/elife.97854","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T11:26:34Z","timestamp":1718796394000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.97854","source":"Crossref","is-referenced-by-count":23,"title":["Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells"],"prefix":"10.7554","volume":"13","author":[{"given":"Yanling","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02xe5ns62","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, School of Medicine, Jinan University","place":["Guangzhou, 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