{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:51:49Z","timestamp":1790794309311,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"High-level talent start-up fund","award":["2022071"],"award-info":[{"award-number":["2022071"]}]},{"name":"High-level talent start-up fund","award":["gzwkj2025-507"],"award-info":[{"award-number":["gzwkj2025-507"]}]},{"name":"Science and Technology Fund of Guizhou Provincial Health Commission","award":["2022071"],"award-info":[{"award-number":["2022071"]}]},{"name":"Science and Technology Fund of Guizhou Provincial Health Commission","award":["gzwkj2025-507"],"award-info":[{"award-number":["gzwkj2025-507"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic \u03b2 cell function remains elusive. This study aimed to explore the impact of uric acid levels on \u03b2 cell function and delineate its underlying molecular mechanisms. Methods: Both in vivo hyperuricemia diet-induced mouse models and in vitro pancreatic \u03b2 cell models were utilized. Results: A progressive decrease in glucose-stimulated insulin secretion and increase in \u03b2 cell apoptosis were observed in the hyperuricemia diet-induced mouse model, and these could be effectively restored by urate-lowering therapy. The dose- and time-dependent direct effects of uric acid on \u03b2 cell apoptosis and insulin secretion were further confirmed in both INS-1E cells and primary isolated islets. Mechanistically, the primary role of expression of the endoplasmic reticulum stress marker C\/EBP homologous protein (CHOP) was detected by RNA sequencing, and the inflammatory factor NLRP3 and pro-apoptotic genes were significantly upregulated by uric acid treatment. Conclusions: Together, our findings indicate a direct crosstalk between uric acid and \u03b2 cells via CHOP\/NLRP3 pathway, providing a new understanding of the diabetogenic effect of uric acid.<\/jats:p>","DOI":"10.3390\/diseases13070213","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T10:03:27Z","timestamp":1751882607000},"page":"213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Uric Acid Causes Pancreatic \u03b2 Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2827-7207","authenticated-orcid":false,"given":"Xueyan","family":"Li","sequence":"first","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Department of Nutrition, School of Public Health of Guizhou Medical University, Guiyang, 561000, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2626-1466","authenticated-orcid":false,"given":"Yunan","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"He","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1089","DOI":"10.1016\/S2468-2667(24)00250-0","article-title":"Diabetes in China part 1: Epidemiology and risk factors","volume":"9","author":"Xu","year":"2024","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the beta cell: The last ten years","volume":"148","author":"Ashcroft","year":"2012","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111805","DOI":"10.1016\/j.diabres.2024.111805","article-title":"Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of beta-cell function","volume":"215","author":"Chen","year":"2024","journal-title":"Diabetes Res. 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