Microcystin-LR impairs glucose metabolism in pancreatic β cells in vivo and in vitro

被引:11
作者
Chen, Yu [1 ]
Chen, Kun [2 ]
Zhou, Yuan [3 ]
Li, Xingjia [1 ]
Mao, Xiaodong [1 ]
Wei, Xiao [1 ]
Xu, Yijiao [1 ]
Yang, Wanwei [4 ]
Chen, Guofang [2 ]
Liu, Chao [2 ]
机构
[1] Nanjing Univ Chinese Med, Res Ctr Endocrinol & Metab Dis, Affiliated Hosp Integrated Tradit Chinese & Weste, Nanjing 210028, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Dept Endocrinol, Affiliated Hosp Integrated Tradit Chinese & Weste, Nanjing 210028, Jiangsu, Peoples R China
[3] Nanjing Univ Chinese Med, Sch Med & Life Sci, Nanjing 210023, Jiangsu, Peoples R China
[4] Nanjing Univ Chinese Med, Clin Lab, Affiliated Hosp Integrated Tradit Chinese & Weste, Nanjing 210028, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Microcystin-LR; Glucose metabolism; beta-Cell function; Oatp; Apoptosis; AIR-POLLUTION; APOPTOSIS; IDENTIFICATION; DYSFUNCTION; PHALLOIDIN; TOXICITY; PATHWAYS;
D O I
10.1016/j.toxlet.2020.03.003
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
This study aimed to investigate the toxic effects of microcystin-LR (MC-LR), which is released from several bloom-forming cyanobacteria, on the glucose metabolism of pancreatic beta cells in vivo and in vitro. Male mice and the pancreatic MIN6 cells were respectively treated with varying concentrations of MC-LR. After 3- or 6-months of MC-LR exposure, increase in the body weight of mice was found to be inhibited, and the structure of their pancreatic tissues was damaged with impaired glucose tolerance and impaired insulin secretion. Further, these toxic effects became more pronounced with time and with increased dosages. Direct cytotoxic effects of MC-LR were observed in the MIN6 pancreatic beta-cells possibly due to their expression of the MC-LR specific transporter. MC-LR entered the MIN6 cells that significantly reduced the cell viability. Both in vivo and in vitro experiments demonstrated that MC-LR was able to induce apoptosis, possibly associated with mitochondrial damage. Above all, these findings implied that MC-LR may be transported into the pancreatic beta cells and cause subsequent cytotoxicity.
引用
收藏
页码:106 / 113
页数:8
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