Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways
Background: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms. Methods: Both in vivo hyperuricemia diet-i...
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MDPI AG
2025-07-01
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| author | Xueyan Li Yunan Chen Lei Su Jialin He |
| author_facet | Xueyan Li Yunan Chen Lei Su Jialin He |
| author_sort | Xueyan Li |
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| description | Background: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms. Methods: Both in vivo hyperuricemia diet-induced mouse models and in vitro pancreatic β cell models were utilized. Results: A progressive decrease in glucose-stimulated insulin secretion and increase in β 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 β 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 β cells via CHOP/NLRP3 pathway, providing a new understanding of the diabetogenic effect of uric acid. |
| format | Article |
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| institution | Matheson Library |
| issn | 2079-9721 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Diseases |
| spelling | doaj-art-1a503382d25b4643b5a8948059e240c42025-07-25T13:20:04ZengMDPI AGDiseases2079-97212025-07-0113721310.3390/diseases13070213Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress PathwaysXueyan Li0Yunan Chen1Lei Su2Jialin He3The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Department of Nutrition, School of Public Health of Guizhou Medical University, Guiyang, 561000, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510000, ChinaBackground: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms. Methods: Both in vivo hyperuricemia diet-induced mouse models and in vitro pancreatic β cell models were utilized. Results: A progressive decrease in glucose-stimulated insulin secretion and increase in β 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 β 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 β cells via CHOP/NLRP3 pathway, providing a new understanding of the diabetogenic effect of uric acid.https://www.mdpi.com/2079-9721/13/7/213uric acidβ cell deathpancreatic β cell dysfunctiontype 2 diabetes |
| spellingShingle | Xueyan Li Yunan Chen Lei Su Jialin He Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways Diseases uric acid β cell death pancreatic β cell dysfunction type 2 diabetes |
| title | Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways |
| title_full | Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways |
| title_fullStr | Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways |
| title_full_unstemmed | Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways |
| title_short | Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways |
| title_sort | uric acid causes pancreatic β cell death and dysfunction via modulating chop mediated endoplasmic reticulum stress pathways |
| topic | uric acid β cell death pancreatic β cell dysfunction type 2 diabetes |
| url | https://www.mdpi.com/2079-9721/13/7/213 |
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