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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance

Authors: Wen-Jun Su, Wei Peng, Hong Gong, Yun-Zi Liu, Yi Zhang, Yong-Jie Lian, Zhi-Yong Cao, Ran Wu, Lin-Lin Liu, Bo Wang, Yun-Xia Wang, Chun-Lei Jiang

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Abundant reports indicated that depression was often comorbid with type 2 diabetes and even metabolic syndrome. Considering they might share common biological origins, it was tentatively attributed to the chronic cytokine-mediated inflammatory response which was induced by dysregulation of HPA axis and overactivation of innate immunity. However, the exact mechanisms remain obscure. Herein, we mainly focused on the function of the NLRP3 inflammasome to investigate this issue.

Methods

Male C57BL/6 mice were subjected to 12 weeks of chronic unpredictable mild stress (CUMS), some of which were injected with glyburide or fluoxetine. After CUMS procedure, behavioral and metabolic tests were carried out. In order to evaluate the systemic inflammation associated with inflammasome activation, IL-1β and inflammasome components in hippocampi and pancreases, as well as corticosterone and IL-1β in serum were detected separately. Moreover, immunostaining was performed to assess morphologic characteristics of pancreases.

Results

In the present study, we found that 12 weeks’ chronic stress resulted in depressive-like behavior comorbid with insulin resistance. Furthermore, antidiabetic drug glyburide, an inhibitor of the NLRP3 inflammasome, was discovered to be effective in preventing the experimental comorbidity. In brief, it improved behavioral performance, ameliorated insulin intolerance as well as insulin signaling in the hippocampus possibly through inhibiting NLRP3 inflammasome activation by suppressing the expression of TXNIP.

Conclusions

All these evidence supported our hypothesis that chronic stress led to comorbidity of depressive-like behavior and insulin resistance via long-term mild inflammation. More importantly, based on the beneficial effects of blocking the activation of the NLRP3 inflammasome, we provided a potential therapeutic target for clinical comorbidity and a new strategy for management of both diabetes and depression.
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Metadata
Title
Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance
Authors
Wen-Jun Su
Wei Peng
Hong Gong
Yun-Zi Liu
Yi Zhang
Yong-Jie Lian
Zhi-Yong Cao
Ran Wu
Lin-Lin Liu
Bo Wang
Yun-Xia Wang
Chun-Lei Jiang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0985-4

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