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01-12-2020 | Chloroquin | Original Article

Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction

Authors: Wenzhen Deng, Yang Li, Ziyu Ren, Qirui He, Yanjun Jia, Yongjian Liu, Weiwei Zhang, Xianfeng Gan, Dongfang Liu

Published in: Endocrine | Issue 3/2020

Abstract

Thioredoxin-interacting protein (TXNIP) is a known important regulatory protein of islet β-cell biology and function, but the detailed mechanism is not clear. Autophagy plays a pivotal role in maintaining cellular homoeostasis. This study aimed to elucidate the influence of TXNIP on the autophagy of β-cell. In this study, C57BL/6 mice and TXNIP^−/− mice were fed with a standard diet (SD) or a high-fat and high-sugar diet (HFSD), and then we analysed biochemical and autophagy related indexes in the mice. We infected MIN6 cells with LV-TXNIP and siRNA TXNIP, then the cells were treated with free fatty acid (FFA), autophagic activator rapamycin (RAP), inhibitors of autophagy chloroquine (CQ) and bafilomycin A1(BAF), finally, we examined the changes of autophagy in MIN6 cells. The results showed that HFSD led to β-cell dysfunction and autophagy dysregulation, which was improved by TXNIP knockout in mice. In vitro experiments, TXNIP gene silencing enhanced LC3B-I conversion to LC3B-II, reduced the protein level of P62, decreased autophagosome accumulation induced by FFA treatment, increased the glucose-stimulated insulin secretion (GSIS) and autophagic flux inhibited by treatment with CQ. TXNIP overexpression induced upregulation of LC3B-I, LC3B-II and P62, accentuating the increase in autophagy and organelle destruction induced by FFA, and exacerbated the effect of BAF on the accumulation of autophagy proteins. Increasing TXNIP levels reduced GSIS, which was reversed by treatment with RAP. In summary, our study suggested that TXNIP is a critical link between autophagy disorders and pancreatic β-cell dysfunction.

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Title: Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction
Authors: Wenzhen Deng
Yang Li
Ziyu Ren
Qirui He
Yanjun Jia
Yongjian Liu
Weiwei Zhang
Xianfeng Gan
Dongfang Liu
Publication date: 01-12-2020
Publisher: Springer US
Keywords: Chloroquin
Insulins
Chloroquin
Insulins
Published in: Endocrine / Issue 3/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-020-02471-6

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