
腸管L細胞に発現するPiezo1チャネルが腸内容物による機械的刺激を感知し、CaMKKβ/CaMKIV-mTORC1シグナル経路を活性化することで、GLP-1の合成と分泌を調節する。


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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. Our study showed 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 ( IntL-Piezo1-/- ) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKKβ/CaMKIV-mTORC1 signaling pathway under normal chow diet or high fed 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 findings suggest a previously undiscovered mechano-regulation of GLP-1 production in L cells, which may shed new light on the treatments of diabetes.

### Competing Interest Statement

The authors have declared no competing interest.

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

腸管l細胞におけるpiezo1によるglp-1産生の機械的調節


腸管L細胞におけるPiezo1によるGLP-1産生の機械的調節
