Zinc and iron dynamics in human islet amyloid polypeptide-induced diabetes mouse model

Author:

Fukunaka Ayako,Shimura Mari,Ichinose Takayuki,Pereye Ofejiro B.,Nakagawa Yuko,Tamura Yasuko,Mizutani Wakana,Inoue Ryota,Inoue Takato,Tanaka Yuto,Sato Takashi,Saitoh Tatsuya,Fukada Toshiyuki,Nishida Yuya,Miyatsuka Takeshi,Shirakawa Jun,Watada Hirotaka,Matsuyama Satoshi,Fujitani Yoshio

Abstract

AbstractMetal homeostasis is tightly regulated in cells and organisms, and its disturbance is frequently observed in some diseases such as neurodegenerative diseases and metabolic disorders. Previous studies suggest that zinc and iron are necessary for the normal functions of pancreatic β cells. However, the distribution of elements in normal conditions and the pathophysiological significance of dysregulated elements in the islet in diabetic conditions have remained unclear. In this study, to investigate the dynamics of elements in the pancreatic islets of a diabetic mouse model expressing human islet amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis of elements using synchrotron scanning X-ray fluorescence microscopy and quantitative analysis of elements using inductively coupled plasma mass spectrometry. We found that in the islets, zinc significantly decreased in the early stage of diabetes, while iron gradually decreased concurrently with the increase in blood glucose levels of hIAPP-Tg mice. Notably, when zinc and/or iron were decreased in the islets of hIAPP-Tg mice, dysregulation of glucose-stimulated mitochondrial respiration was observed. Our findings may contribute to clarifying the roles of zinc and iron in islet functions under pathophysiological diabetic conditions.

Funder

Grant-in-Aid for Scientific Research on Innovative Areas “Integrated Bio-metal Science”

joint research program of the Institute for Molecular and Cellular Regulation, Gunma University

Secom Science and Technology Foundation

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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