Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance
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 dysreg...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0985-4 |
| _version_ | 1818243450512867328 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wen-Jun Su |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T14:01:19Z |
| format | Article |
| id | doaj.art-021e5459c7d241fdbac3c726a06e1198 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-12T14:01:19Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-021e5459c7d241fdbac3c726a06e11982022-12-22T00:22:19ZengBMCJournal of Neuroinflammation1742-20942017-10-0114111210.1186/s12974-017-0985-4Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistanceWen-Jun Su0Wei Peng1Hong Gong2Yun-Zi Liu3Yi Zhang4Yong-Jie Lian5Zhi-Yong Cao6Ran Wu7Lin-Lin Liu8Bo Wang9Yun-Xia Wang10Chun-Lei Jiang11Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityDepartment of Psychiatry, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityLaboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12974-017-0985-4DepressionInsulin resistanceGlyburideNLRP3 inflammasomeStressInflammation |
| spellingShingle | 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 Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance Journal of Neuroinflammation Depression Insulin resistance Glyburide NLRP3 inflammasome Stress Inflammation |
| title | Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance |
| title_full | Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance |
| title_fullStr | Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance |
| title_full_unstemmed | Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance |
| title_short | Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance |
| title_sort | antidiabetic drug glyburide modulates depressive like behavior comorbid with insulin resistance |
| topic | Depression Insulin resistance Glyburide NLRP3 inflammasome Stress Inflammation |
| url | http://link.springer.com/article/10.1186/s12974-017-0985-4 |
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