中国药理学通报2025，Vol.41Issue(7)：1273-1282,10.DOI:10.12360/CPB202410009
过表达PP2Cm减轻阿托伐他汀诱导的胰岛素抵抗
Overexpression of PP2Cm alleviates atorvastatin-induced insulin resistance
摘要
Abstract
Aim To investigate the potential role and related mechanisms of protein phosphatase 2Cm(PP2Cm)overexpression in atorvastatin-induced insu-lin resistance.Methods Male C57BL/6J mice,fibro-blast growth factor 21 knockout(FGF21-KO)mice,and wildtype(WT)mice were raised for 12 weeks to construct models.Groups included atorvastatin,con-trol,atorvastatin+PP2Cm overexpression(OE),FGF21-KO+vehicle,FGF21-KO+PP2Cm OE,WT+vehicle,WT+PP2Cm OE.Body weight,fasting blood glucose levels,fasting insulin levels,and intraperitoneal glucose tolerance tests(IPGTT)were measured in 4,8 and 12 weeks.The concentrations of branched-chain a-mino acids(BCAA)in cells,tissues and serum,as well as the mRNA and protein expression of BCAA cat-abolic enzymes,were determined by qRT-PCR,Western blot and ELISA after atorvastatin treatment.Further-more,the effects of PP2Cm overexpression on these in-dicators were explored,and the FGF21 was verified in vivo and in vitro.Results Atorvastatin induced insu-lin resistance in mice,altered insulin,glucose tolerance and increased BCAA levels.PP2Cm overexpression mitigated these changes.In the Atorvastatin+PP2Cm OE group,FGF21 mRNA,protein and concentration were all significantly upregulated.Regardless of PP2Cm overexpression,the knockout of FGF21 signifi-cantly increased BCAA expression levels,both fasting insulin and blood glucose levels were significantly high-er than those in WT group.Conclusions FGF21 may be an important regulator of PP2Cm involved in atorv-astatin-induced insulin resistance.PP2Cm overexpres-sion alleviates the effects of atorvastatin-induced insulin resistance by regulating FGF21.关键词
阿托伐他汀/胰岛素抵抗/支链氨基酸/蛋白磷酸酶2Cm/成纤维细胞生长因子21/支链-酮酸脱氢酶Key words
atorvastatin/insulin resistance/branched-chain amino acid/protein phosphatase 2Cm/fibroblast growth factor 21/branched chain alpha-ketoate dehy-drogenase分类
医药卫生引用本文复制引用
赵诗晗,唐才林,陈宇,黄伟康,罗凤蓉,白雪..过表达PP2Cm减轻阿托伐他汀诱导的胰岛素抵抗[J].中国药理学通报,2025,41(7):1273-1282,10.基金项目
中国药学会-施维雅青年医院药学创新资助项目(No CPA-B04-ZC-2024-001) （No CPA-B04-ZC-2024-001）
