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GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study

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收录情况： ◇ SCIE

作者：
Gao Yang[1,2] * ; Yu Haitao[3] * ; Liu Yanchao[4] ; Xu Zhipeng[5] ; He Benrong[1] ; Liu Honghai[6] ; Wang Yuying[1] ; Zhang Yao[7] ; Liang Yi[2] ; Yang Ying[1] ; Zheng Jie[8,*1] ; Wang Jian-Zhi[1,9,*2] ;
单位： [1]Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [2]Department of Radiology, Wuhan Brain Hospital, Wuhan, China. [3]Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China. [4]Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [5]Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China. [6]School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [7]Li-Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [8]Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University , Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, China. [9]Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
出处：
DOI： 10.1111/1753-0407.13470
ISSN：

关键词： ApoE gene polymorphism glycogen synthase kinase-3β mediation analyses mild cognitive impairment type 2 diabetes mellitus

摘要：
Both the activation of glycogen synthase kinase-3β (GSK-3β) and the presence of ApoE ε4 genotype have been found to respectively correlate with cognitive decline in patients with type 2 diabetes mellitus (T2DM), who further show a high incidence of developing Alzheimer's disease. However, the relationship between ApoE ε4 and GSK-3β in the cognitive impairment of T2DM patients remains unclear.ApoE genotypes and platelet GSK-3β level were measured in 1139 T2DM patients recruited from five medical centers in Wuhan, China. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). The association and the relationships among apolipoprotein E (ApoE) genotypes, GSK-3β activity and cognitive function were analyzed by regression and mediating effect analyses, respectively.T2DM patients with ApoE ε4 but not ApoE ε2 haplotype showed poorer cognitive function and elevated platelet GSK-3β activity, when using ApoE ε3 as reference. The elevation of GSK-3β activity was positively correlated the diabetes duration, as well as plasma glycated hemoglobin (HbA1c) and glucose levels. Moreover, correlation and regression analysis also revealed significant pairwise correlations among GSK-3β activity, ApoE gene polymorphism and cognitive function. Lastly, using Baron and Kenny modeling, we unveiled a mediative role of GSK-3β activity between ApoE ε4 and cognitive impairment.We reported here that the upregulation of GSK-3β activity mediates the exacerbation of cognitive impairment by ApoE ε4-enhanced cognitive impairment in T2DM patients, suggesting GSK-3β inhibitors as promising drugs for preserving cognitive function in T2DM patients, especially to those with ApoE ε4 genotype.© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

基金：
Guangdong Provincial Key S&T Program, Grant/Award Number: 018B030336001;National Key R&D Program of China, Grant/Award Numbers: 2016YFC1305800, 2018ACA142; Natural Science Foundation of China, Grant/Award Numbers: 31730035, 81721005, 81901107, 91949205; Wuhan Health Science Foundation, Grant/Award Number: WX20Q04; Fundamental Research Funds for the Central Universities, Grant/Award Number: YCJJ202203019; Hubei Province scientific research project, Grant/Award Number: WJ2021M041
语种：
外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 医学
小类 | 3 区 内分泌学与代谢
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 内分泌学与代谢
JCR分区：
出版当年[2022]版：
Q2 ENDOCRINOLOGY & METABOLISM
最新[2023]版：
Q2 ENDOCRINOLOGY & METABOLISM

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [2]Department of Radiology, Wuhan Brain Hospital, Wuhan, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [8]Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University , Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, China. [9]Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. [*1]Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University , Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, China [*2]Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
推荐引用方式(GB/T 7714)：
Gao Yang,Yu Haitao,Liu Yanchao,et al.GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study[J].JOURNAL OF DIABETES.2024,16(1):doi:10.1111/1753-0407.13470.
APA：
Gao Yang,Yu Haitao,Liu Yanchao,Xu Zhipeng,He Benrong...&Wang Jian-Zhi.(2024).GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study.JOURNAL OF DIABETES,16,(1)
MLA：
Gao Yang,et al."GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study".JOURNAL OF DIABETES 16..1(2024)

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