Infection with SARS-CoV-2 can cause pancreatic impairment  

作　　者：Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin 

机构地区：[1]NHC Key Laboratory of Comparative Medicine,Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Comparative Medicine Center,Peking Union Medical College,Beijing 100021,China [2]Institute of Molecular Medicine,College of Future Technology,Peking University,Beijing 100871,China [3]Beijing Key Laboratory of Cardiometabolic Molecular Medicine,Peking University,Beijing 100871,China [4]State Key Laboratory of Biomembrane and Membrane Biotechnology,Peking-Tsinghua Center for Life Sciences,Beijing 100871,China [5]Chinese Academy of Engineering,Eastern Hepatobiliary Surgery Hospital,225 Changhai Road,Yangpu District,Shanghai 200438,China [6]International Co-operation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Institute,Second Military Medical University,Shanghai 200438,PR China [7]National Laboratory for Oncogenes and Related Genes,Cancer Institute of Shanghai Jiao Tong University,Shanghai 200441,PR China [8]Changping National laboratory(CPNL),Beijing 102206,China [9]State Key Laboratory of Respiratory Health and Multimorbidity,National Health Commission of the People’s Republic of China,Beijing,PR China

出　　处：《Signal Transduction and Targeted Therapy》2024年第5期2143-2160,共18页信号转导与靶向治疗（英文）

基　　金：supported by the Institute of Basic Medical Sciences,the Chinese Academy of Medical Sciences,the Neuroscience Center,the China Human Brain Banking Consortium,the ALS Brain Bank Initiative in China,and Home for Heal and Help for their assistance in this paper.This work was supported by the National Natural Science Foundation of China(82141204,82061138007,82221004,82041008);the National Key Research and Development Project of China(2020YFA0707803);the CAMS Innovation Fund for Medical Sciences(CIFMS)grant(2021-1-I2M-035,2021-1-I2M-034 and 2021-CAMS-JZ002);Bill&Melinda Gates Foundation(INV-006371);Key-Area Research and Development Program of Guangdong Province(2022B1111020005).

摘　　要：Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关 键 词：INFECTED ELEVATED HOMEOSTASIS 

分 类 号：R576[医药卫生—消化系统]