JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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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

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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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400013

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author="Haipeng CHENG, Zhenwang ZHAO, Dan LIU, Yufei WANG, Min ZHANG",
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year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2400013"
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%T Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes
%A Haipeng CHENG
%A Zhenwang ZHAO
%A Dan LIU
%A Yufei WANG
%A Min ZHANG
%J Journal of Zhejiang University SCIENCE B
%P 796-799
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doi="https://doi.org/10.1631/jzus.B2400013"

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T1 - Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes
A1 - Haipeng CHENG
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A1 - Dan LIU
A1 - Yufei WANG
A1 - Min ZHANG
J0 - Journal of Zhejiang University Science B
SP - 796
EP - 799
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2400013"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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。

关键词组：未折叠蛋白应答（UPR）；衰老；1型糖尿病（T1D）

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Reference

[1]EnginF, YermalovichA, NguyenT, et al., 2013. Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes. Sci Transl Med, 5(211):211ra156.

[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.

[4]LeeH, SahinGS, ChenCW, et al., 2023. Stress-induced β cell early senescence confers protection against type 1 diabetes. Cell Metab, 35(12):2200-2215.e9.

[5]LeendersF, GroenN, de GraafN, et al., 2021. Oxidative stress leads to β‍-cell dysfunction through loss of β‍-cell identity. Front Immunol, 12:690379.

[6]MakamAA, BiswasA, KothegalaL, et al., 2022. Setting the stage for insulin granule dysfunction during type-1-diabetes: is ER stress the culprit? Biomedicines, 10(11):2695.

[7]MoritaS, VillaltaSA, FeldmanHC, et al., 2017. Targeting ABL-IRE1α signaling spares ER-stressed pancreatic β cells to reverse autoimmune diabetes. Cell Metab, 25(4):883-897.e8.

[8]Paramos-de-CarvalhoD, JacintoA, SaúdeL, 2021. The right time for senescence. Elife, 10:e72449.

[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.

[10]RuiJX, DengSY, AraziA, et al., 2017. β Cells that resist immunological attack develop during progression of autoimmune diabetes in NOD mice. Cell Metab, 25(3):‍727-738.

[11]ShanB, WangXX, WuY, et al., 2017. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity. Nat Immunol, 18(5):519-529.

[12]SturmlechnerI, ZhangC, SineCC, et al., 2021. P21 produces a bioactive secretome that places stressed cells under immunosurveillance. Science, 374(6567):eabb3420.

[13]SyedFZ, 2022. Type 1 diabetes mellitus. Ann Intern Med, 175(3):ITC33-ITC48.

[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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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

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