1. Academic Validation
  2. Pancreatic islet-autonomous effect of arsenic on insulin secretion through endoplasmic reticulum stress-autophagy pathway

Pancreatic islet-autonomous effect of arsenic on insulin secretion through endoplasmic reticulum stress-autophagy pathway

  • Food Chem Toxicol. 2018 Jan;111:19-26. doi: 10.1016/j.fct.2017.10.043.
Wei Wu 1 Xiaofeng Yao 1 Liping Jiang 2 Qiaoting Zhang 1 Jie Bai 1 Tianming Qiu 1 Lei Yang 1 Ni Gao 1 Guang Yang 1 Xiaofang Liu 1 Min Chen 1 Xiance Sun 3
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
  • 2 Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
  • 3 Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China. Electronic address: sunxiance@dmu.edu.cn.
Abstract

Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated Insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly. After treatment with NaAsO2, the p-PERK level in INS-1 rat pancreatic β- cells was increased correspondingly. After treatment with PERK Inhibitor, the GSIS from isolated pancreatic islets of As2O3-treated mice was recovered. Arsenic induced Autophagy in pancreatic islets, as evidenced by elevated LC3-II level and depressed p62 level in vivo and in vitro. In NaAsO2-treated INS-1 cells, the initiation of ER stress preceded the stimulation of Autophagy, which was a key factor controlling pancreatic β cell function. Furthermore, knockdown of PERK attenuated NaAsO2-induced Autophagy in INS-1 cells. These data indicated that arsenic impaired β cell function through ER stress-autophagy pathway. The present study will provide new mechanistic insights into arsenic-related diabetes.

Keywords

Arsenic; Autophagy; Endoplasmic reticulum stress; Insulin secretion; PERK.

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