Protective effects of curcumin on desipramine-induced isletβ-cell damage via AKAP150/PKA/PP2B complex  

作　　者：Min Hu Jia-ying Cai Yao He Kui Chen Feng Hao Jin-sen Kang Yan Pan Lu Tie Xue-jun Li 

机构地区：[1]Department of Pharmacology,School of Basic Medical Sciences,Peking University&Beijing Key Laboratory of Tumor Systems Biology,Peking University,Beijing 100191,China [2]Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China [3]Department of Pharmacology,School of Pharmacy,Shihezi University,Shihezi 832002,China

出　　处：《Acta Pharmacologica Sinica》2024年第2期327-338,共12页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.92168120,81974506,81673486 and 81373405 to Lu Tie,No.82073878,81020108031 and 81874318 to Xue-jun Li);the Beijing Natural Science Foundation(No.Z200019 and 7172119)to Lu Tie.

摘　　要：Tricyclic antidepressants(TCAs)are widely used to treat depression and anxiety-related mood disorders.But evidence shows that TCAs elevate blood glucose levels and inhibit insulin secretion,suggesting that TCAs are a risk factor,particularly for individuals with diabetes.Curcumin is a bioactive molecule from the rhizome of the Curcuma longa plant,which has shown both antidepressant and anti-diabetic activities.In the present study,we investigated the protective effect of curcumin against desipramine-induced apoptosis inβcells and the underlying molecular mechanisms.In the mouse forced swimming test(FST),we found that lower doses of desipramine(5 and 10 mg/kg)or curcumin(2.5 mg/kg)alone did not affect the immobility time,whereas combined treatment with curcumin(2.5 mg/kg)and desipramine(5,10 mg/kg)significantly decreased the immobility time.Furthermore,desipramine dose-dependently inhibited insulin secretion and elevated blood glucose levels,whereas the combined treatment normalized insulin secretion and blood glucose levels.In RIN-m5F pancreaticβ-cells,desipramine(10μM)significantly reduced the cell viability,whereas desipramine combined with curcumin dose-dependently prevented the desipramine-induced impairment in glucose-induced insulin release,most effectively with curcumin(1 and 10μM).We demonstrated that desipramine treatment promoted the cleavage and activation of Caspase 3 in RIN-m5F cells.Curcumin treatment inhibited desipramine-induced apoptosis,increased mitochondrial membrane potential and Bcl-2/Bax ratio.Desipramine increased the generation of reactive oxygen species,which was reversed by curcumin treatment.Curcumin also inhibited the translocation of forkhead box protein O1(FOXO1)from the cytoplasm to the nucleus and suppressed the binding of A-kinase anchor protein 150(AKAP150)to protein phosphatase 2B(PP2B,known as calcineurin)that was induced by desipramine.These results suggest that curcumin protects RIN-m5F pancreaticβ-cells against desipramine-induced apoptosis by inhibiting the phosphoino

关 键 词：tricyclic antidepressants DESIPRAMINE insulin secretion 

分 类 号：R96[医药卫生—药理学]