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《中国生理学会内分泌代谢、比较生理与应激生理学术会议论文摘要汇编》2017年
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Antidiabetic Drug Glyburide Modulate Depressive-like Behavior Comorbid with Insulin Resistance Induced by Chronic Stress

Wen-Jun SU  Chun-Lei JIANG  
【摘要】:Objective Abundant reports indicated that Depression was often comorbid with Type 2 Diabetes,and even Metabolic Syndrome.Considering there might be common biological origins between them,it was tentatively attributed to the chronic cytokine-mediated inflammatory response which induced by dysregulation of HPA axis and overactivation of innate immunity.However,the exact mechanisms still remain obscure.Herein,we investigated this issue mainly concentrate on the function of NLRP3 inflammasome.Methods Male C57 BL/6 mice were subjected to chronic unpredictable mild stress(CUMS) for 12 weeks,some of them were injected simultaneously with Glyburide or Fluoxetine.After CUMS procedure,behavioral tests including sucrose preference tests,tail suspension tests and open field tests were carried out.Meanwhile,metabolic parameters including glucose tolerance tests,insulin tolerance tests and glucose-stimulated insulin secretion tests were also conducted.In order to evaluate the inflammasome related systemic inflammation,IL-1β,inflammasome components including NLRP3,caspase-1 p10 in pancreases and hippocampi,as well as corticosterone and IL-1β in serum were detected.Moreover,immunostaining and analyses were performed,aiming at measuring morphologic characteristics of pancreases.Results In the present research,we found that 12 weeks' chronic stress resulted in depressive-like behavior comorbid with insulin resistance.Furthermore,as a compound that inhibiting the activation of NLRP3 inflammasome,antidiabetic drug Glyburide was discovered to prevent the experimental comorbidity.In brief,it improved behavioral performance,attenuated insulin intolerance as well as insulin signaling in the hippocampus possibly via inhibiting NLRP3 inflammasome activation by suppressing TXNIP expression.Besides,it seemed that antidepressant fluoxetine could limitedly modulate insulin insensitivity and secretion somehow.Conclusion All these evidences supported our hypothesis mat chronic stress induced comorbidity of depressive-like behavior and insulin resistance by activation NLRP3 inflammasome.More importantly,we provided a potential therapeutic target for clinical comorbid patients and a new strategy for management of diabetes and depression.
【作者单位】:Laboratory of Stress Medicine,Faculty of Psychology and Mental Health,Second Military Medical University
【分类号】:R587.1;R749.4
【正文快照】:
Antidiabetic Drug Glyburide Modulate Depressive-like Behavior Comorbid with Insulin Resistance Induced by Chronic Stress@Wen-Jun SU$Laboratory of Stress Medicine,Faculty of Psychology and Mental Health,Second Military Medical University!800 Xiangyin Road

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