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This study aims to employ a drug repurposing strategy to screen GPR119 agonists and explore their potential molecular mechanisms for enhancing \u03b2\u2010cell function in the context of NAFPD. MIN6 cells were stimulated with palmitic acid (PA), and a NAFPD model was established in GPR119<jats:sup>\u2212\/\u2212<\/jats:sup> mice fed with a high\u2010fat diet (HFD). Terazosin, identified through screening, was utilized to assess its impact on enhancing \u03b2\u2010cell function via the MST1\u2010Foxo3a pathway and mitophagy. Terazosin selectively activated GPR119, leading to increased cAMP and ATP synthesis, consequently enhancing insulin secretion. Terazosin administration improved high blood glucose, obesity, and impaired pancreatic \u03b2\u2010cell function in NAFPD mice. It inhibited the upregulation of MST1\u2010Foxo3a expression in pancreatic tissue and enhanced damaged mitophagy clearance, restoring autophagic flux, and improving mitochondrial quantity and structure in \u03b2\u2010cells. Nevertheless, GPR119 deficiency negated the positive impact of terazosin on pancreatic \u03b2\u2010cell function in NAFPD mice and abolished its inhibitory effect on the MST1\u2010Foxo3a pathway. Terazosin activates GPR119 on the surface of pancreatic \u03b2\u2010cells, enhancing mitophagy and alleviating \u03b2\u2010cell dysfunction in the context of NAFPD by suppressing the MST1\u2010Foxo3a signalling pathway. Terazosin could be considered a priority treatment for patients with concomitant NAFPD and hypertension.<\/jats:p>","DOI":"10.1111\/cpr.13764","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T16:40:03Z","timestamp":1729096803000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Terazosin, a repurposed <scp>GPR119<\/scp> agonist, ameliorates mitophagy and \u03b2\u2010cell function in <scp>NAFPD<\/scp> by inhibiting <scp>MST1<\/scp>\u2010Foxo3a signalling pathway"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-0040","authenticated-orcid":false,"given":"Chenglei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Ningxia Medical University  Yinchuan Ningxia China"},{"name":"Medical Laboratory General Hospital of Ningxia Medical University  Yinchuan Ningxia 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