期刊
FRONTIERS IN ENDOCRINOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.624309
关键词
SNAPIN; beta cells; proliferation; cell cycle; diabetes
资金
- Natural Science Foundation of China [81471081, 91953114, 81761128015, 81861130370, 31871319]
- Natural Science Foundation of Fujian Province, China [2019J01010]
- Xiamen Research Foundation for Science and Technology Project [3502Z20194037]
- Scientific Research Foundation for Advanced Talents, Xiang'an Hospital of Xiamen University [PM201809170005]
This study reveals that SNAPIN plays a crucial role in regulating insulin secretion and beta cell proliferation, with its expression influenced by age and diabetes. The function of SNAPIN is achieved through its impact on cell cycle regulation, suggesting it might be a potential pharmacotherapeutic target for diabetes mellitus.
In diabetes mellitus, death of beta cell in the pancreas occurs throughout the development of the disease, with loss of insulin production. The maintenance of beta cell number is essential to maintaining normoglycemia. SNAPIN has been found to regulate insulin secretion, but whether it induces beta cell proliferation remains to be elucidated. This study aimed to explore the physiological roles of SNAPIN in beta cell proliferation. SNAPIN expression increases with the age of mice and SNAPIN is down-regulated in diabetes. KEGG pathway and GO analysis showed that SNAPIN- interacting proteins were enriched in cell cycle regulation. B cell cycle was arrested in the S phase, and cell proliferation was inhibited after SNAPIN knockdown. The expression of CDK2, CDK4 and CCND1 proteins in the S phase of the cell cycle were reduced after SNAPIN knockdown, whereas they were increased after overexpression of SNAPIN. In addition, insulin protein and mRNA levels also increased or decreased after SNAPIN knockdown or overexpression, respectively. Conclusions: Our data indicate that SNAPIN mediates beta cells proliferation and insulin secretion, and provide evidences that SNAPIN might be a pharmacotherapeutic target for diabetes mellitus.
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