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This study aimed to elucidate the altered signaling elicited by Piezo1 activation in the arteries of type 2 diabetes. Ten- to 12-week-old male C57BL\/6 (control) and type 2 diabetic mice (db<jats:sup>\u2212<\/jats:sup>\/db<jats:sup>\u2212<\/jats:sup>) were used. The second-order mesenteric arteries (~ 150 \u03bcm) were used for isometric tension experiments. Western blot analysis and immunofluorescence staining were performed to observe protein expression. Piezo1 was significantly decreased in mesenteric arteries of type 2 diabetic mice compared to control mice, as analyzed by western blot and immunofluorescence staining. Piezo1 agonist, Yoda1, concentration-dependently induced relaxation of mesenteric arteries in both groups. Interestingly, the relaxation response was significantly greater in control mice than in db<jats:sup>\u2212<\/jats:sup>\/db<jats:sup>\u2212<\/jats:sup> mice. The removal of endothelium reduced relaxation responses induced by Yoda1, which was greater in control mice than db<jats:sup>\u2212<\/jats:sup>\/db<jats:sup>\u2212<\/jats:sup> mice. Furthermore, the relaxation response was reduced by pre-treatment with various types of K<jats:sup>+<\/jats:sup> channel blockers in endothelium-intact arteries in control mice. In endothelium-denuded arteries, pre-incubation with charybdotoxin, an Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup> channel (BK<jats:sub>Ca<\/jats:sub> channel) blocker, significantly attenuated Yoda1-induced relaxation in db<jats:sup>\u2212<\/jats:sup>\/db<jats:sup>\u2212<\/jats:sup> mice, while there was no effect in control mice. Co-immunofluorescence staining showed co-localization of Piezo1 and BK<jats:sub>Ca<\/jats:sub> channel was more pronounced in db<jats:sup>\u2212<\/jats:sup>\/db<jats:sup>\u2212<\/jats:sup> mice than in control mice. These results indicate that the vascular responses induced by Piezo1 activation are different in the mesenteric resistance arteries in type 2 diabetic mice.<\/jats:p>","DOI":"10.1007\/s00424-024-02983-4","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T16:02:13Z","timestamp":1719936133000},"page":"1479-1492","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Alteration of Piezo1 signaling in type 2 diabetic mice: focus on endothelium and BKCa channel"],"prefix":"10.1007","volume":"476","author":[{"given":"Chae Eun","family":"Haam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooyeon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonhee","family":"Byeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Yi","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Kyoung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"issue":"11","key":"2983_CR1","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.1161\/ATVBAHA.119.313348","volume":"39","author":"DJ Beech","year":"2019","unstructured":"Beech DJ, Kalli AC (2019) Force sensing by piezo channels in cardiovascular health and disease. 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