Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance
| Autor: | Yi Zhang, Chun-Lei Jiang, Wei Peng, Ran Wu, Bo Wang, Hong Gong, Yun-Xia Wang, Yun-Zi Liu, Wen-Jun Su, Yong-Jie Lian, Lin-Lin Liu, Zhi-Yong Cao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty medicine.medical_treatment Immunology Comorbidity Type 2 diabetes Systemic inflammation Stress lcsh:RC346-429 Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Insulin resistance Internal medicine Glyburide medicine Animals Hypoglycemic Agents Chronic stress lcsh:Neurology. Diseases of the nervous system Inflammation Depressive Disorder biology business.industry Depression Research General Neuroscience Insulin Inflammasome medicine.disease NLRP3 inflammasome Mice Inbred C57BL Insulin receptor 030104 developmental biology Endocrinology Neurology biology.protein medicine.symptom Metabolic syndrome business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-12 (2017) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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