Zinc Chelator Inhibits Zinc-Induced Islet Amyloid Polypeptide Deposition and Apoptosis in INS-1 Cells

Biological Trace Element Research
He Tian, Zhan-You Wang

Abstract

Amyloid deposition and beta cell apoptosis are characteristic pathological features of type 2 diabetes mellitus (DM). Islet amyloid polypeptide (IAPP) is the most abundant component of amyloid deposition. Monomeric IAPP does not form amyloid deposition, but the fibrous IAPP may aggregate and form amyloid deposits. Previous studies have shown that zinc is closely related to IAPP deposition through crosslink with monomeric IAPP into fibrous aggregates. In this study, we aimed to investigate whether chelating zinc could inhibit zinc-induced amyloid deposits and apoptosis of islet beta cell. N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) is a specific chelator of zinc, with membrane permeability. It could effectively reduce the concentration of intracellular zinc. So, we used TPEN to treat hIAPP-transfected INS-1 cells. By MTT assay, the concentration (1 μM) and incubation time (12 h) of TPEN without affecting cell viability were determined. The results showed that TPEN reduced zinc-induced IAPP deposition in the culture system. Furthermore, we analyzed the effect of zinc and TPEN on the apoptosis and insulin level. The results showed that TPEN could reverse zinc-induced INS-1 cell apoptosis and insulin secretion. A...Continue Reading

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Citations

Nov 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chung-Ze WuJin-Shuen Chen

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Methods Mentioned

BETA
fluorescence microscopy
ELISA
Flow cytometry

Software Mentioned

Image
Flow Jo
Pro Plus
Treestar

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis