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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.9 P.796-799

http://doi.org/10.1631/jzus.B2400013


Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes


Author(s):  Haipeng CHENG, Zhenwang ZHAO, Dan LIU, Yufei WANG, Min ZHANG

Affiliation(s):  Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410011, China; more

Corresponding email(s):   mzhangusc@126.com, 11883@hbuas.edu.cn

Key Words:  Type 1 diabetes (T1D), Senescence, Unfolded protein response (UPR), Pancreatic β, cells


Haipeng CHENG, Zhenwang ZHAO, Dan LIU, Yufei WANG, Min ZHANG. Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes[J]. Journal of Zhejiang University Science B, 2024, 25(9): 796-799.

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Abstract: 
type 1 diabetes (T1D) is a T lymphocyte-mediated autoimmune disease caused by pancreatic β‍-cell destruction, which eventually leads to reduced insulin level and increased blood glucose level (Syed, 2022). As a multifactorial disease, T1D is characterized by a genetic predisposition associated with various environmental and cellular elements (Syed, 2022). Pancreatic β cells have long been considered the “innocent victims” in T1D pathogenesis since the pancreas is attacked by the immune cells, resulting in a process known as insulitis, in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory cytokines. However, growing evidence suggests that various β‍-cell stresses, dysfunction, and death contribute to T1D pathogenesis, as it has been observed that β‍-cell dysfunction in autoantibody-positive (Aab+) individuals exists long before T1D diagnosis (Evans-Molina et al., 2018).

未折叠蛋白应答缺失导致的胰岛β细胞早期衰老可预防1型糖尿病

成海鹏1,赵真旺3,4,刘丹5,王宇菲3,4,张敏2
1中南大学湘雅二医院病理科,中国长沙市,410011
2南华大学衡阳医学院,心血管疾病研究所,动脉硬化学湖南省重点实验室,湖南省动脉硬化性疾病国际科技创新合作基地,生物信息与医学大数据教研室,中国衡阳市,421001
3湖北文理学院医学部基础医学院,中国襄阳市,441053
4桂林医学院广西糖尿病系统医学科学重点实验室,中国桂林市,541199
5广东省人民医院珠海医院(珠海市金湾中心医院)医务部,中国珠海市,519041
摘要:1型糖尿病(T1D)是T细胞介导的自身免疫性疾病,可导致胰腺β细胞的破坏和胰岛素分泌的不足。内质网(ER)是负责蛋白质合成、加工和分泌的重要细胞器。蛋白质合成的大量需求与蛋白质折叠能力之间的不平衡会导致ER应激,并过度激活未折叠蛋白应答(UPR)的三条经典通路:肌醇需求酶1α(IRE1α)、激活转录因子6(ATF6)和蛋白激酶RNA样内质网激酶(PERK)。为了探究UPR在T1D中的作用,有研究表明在非肥胖型糖尿病(NOD)小鼠的β细胞中特异性敲除ATF6和IRE1α会引起β细胞早期衰老,进一步改变β细胞的衰老相关分泌表型,继而募集M2型巨噬细胞至胰岛。最终,M2型巨噬细胞将促进免疫监视并清除终末衰老的β细胞,从而保护β细胞功能并降低T1D发病率。

关键词:未折叠蛋白应答(UPR);衰老;1型糖尿病(T1D)

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Reference

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[2]Evans-MolinaC, SimsEK, DimeglioLA, et al., 2018. β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis. JCI Insight, 3(15):e120877.

[3]LeeH, LeeYS, HarendaQ, et al., 2020. Beta cell dedifferentiation induced by IRE1α deletion prevents type 1 diabetes. Cell Metab, 31(4):822-836.e5.

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[9]ParsaR, AndresenP, GillettA, et al., 2012. Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice. Diabetes, 61(11):2881-2892.

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[14]ThompsonPJ, ShahA, NtranosV, et al., 2019. Targeted elimination of senescent beta cells prevents type 1 diabetes. Cell Metab, 29(5):1045-1060.e10.

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