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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eLife Sciences Publications Ltd
2024-11-01
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| Online Access: | https://elifesciences.org/articles/97854 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yanling Huang |
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| description | 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. |
| format | Article |
| id | doaj-art-eb257dc2f9fd413daa5bdd3902f61cde |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-eb257dc2f9fd413daa5bdd3902f61cde2025-08-20T02:49:36ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.97854Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cellsYanling Huang0Haocong Mo1https://orcid.org/0009-0009-4778-8062Jie Yang2Luyang Gao3https://orcid.org/0009-0005-6735-5353Tian Tao4Qing Shu5Wenying Guo6Yawen Zhao7Jingya Lyu8Qimeng Wang9Jinghui Guo10Hening Zhai11Linyan Zhu12Hui Chen13https://orcid.org/0000-0002-7218-9047Geyang Xu14https://orcid.org/0000-0002-5542-1350Department of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Pathology, School of Basic Medicine, Guangzhou Medical University, Guangdong, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, ChinaBiotherapy Center, Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaSchool of Medicine, The Chinese University of Hong Kong, Shenzhen, ChinaEndoscopy Center, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Pharmacology, School of Medicine, Jinan University, Guangzhou, ChinaBiotherapy Center, Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Physiology, School of Medicine, Jinan University, Guangzhou, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou, ChinaGlucagon-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.https://elifesciences.org/articles/97854Piezo1glucagon-like peptide 1intestinal L cellsCaMKKβCaMKIVmechanistic target of rapamycin |
| spellingShingle | 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 Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells eLife Piezo1 glucagon-like peptide 1 intestinal L cells CaMKKβ CaMKIV mechanistic target of rapamycin |
| title | Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells |
| title_full | Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells |
| title_fullStr | Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells |
| title_full_unstemmed | Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells |
| title_short | Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells |
| title_sort | mechano regulation of glp 1 production by piezo1 in intestinal l cells |
| topic | Piezo1 glucagon-like peptide 1 intestinal L cells CaMKKβ CaMKIV mechanistic target of rapamycin |
| url | https://elifesciences.org/articles/97854 |
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