The role of peripheral β-amyloid in insulin resistance, insulin secretion, and prediabetes: in vitro and population-based studies

Frontiers in Endocrinology

Endocrinology

Jian Xu¹  Xiaoxing Mo²  Hongjie Liu²  Liegang Liu²  Shan Hu²  Xiaobo Peng²  Linyan Li²  Juan Chen²  Zhilei Shan²  Pei Wang²  Zihui Xu²  Yue Huang²  Hong Yan³  Di Wang⁴ 

[1]Department of Elderly Health Management, Shenzhen Center for Chronic Disease Control, Shenzhen, China

[2]Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

[3]Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

[4]Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

[5]Xiangyang Key Laboratory of Public Health and Epidemic Prevention Materials Research, Xiangyang Public Inspection and Testing Center, Xiangyang, China

关键词: peripheral β-amyloid;    in vitro;    insulin resistance;    insulin secretion;    prediabetes;    population-based study;   

DOI  :  10.3389/fendo.2023.1195658

 received in 2023-03-28, accepted in 2023-07-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPrevious experimental studies have shown that mice overexpressing amyloid precursor protein, in which β-amyloid (Aβ) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Aβ on insulin action and insulin secretion in vitro and the association of plasma Aβ with prediabetes in human.MethodsWe examined the effects of Aβ40 and Aβ42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses.ResultsIn the in vitro studies, Aβ40 and Aβ42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Aβ40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Aβ42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Aβ40 and Aβ42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively.ConclusionElevated plasma Aβ40 and Aβ42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic β-cells.

【 授权许可】

Unknown   
Copyright © 2023 Xu, Chen, Wang, Li, Hu, Liu, Huang, Mo, Yan, Shan, Wang, Xu, Liu and Peng