Overexpression of PP2Cm alleviates atorvastatin-induced insulin resistance
- VernacularTitle:过表达PP2Cm减轻阿托伐他汀诱导的胰岛素抵抗
- Author:
Shi-han ZHAO
1
;
Cai-lin TANG
;
Yu CHEN
;
Wei-kang HUANG
;
Feng-rong LUO
;
Xue BAI
Author Information
- Publication Type:Journal Article
- Keywords: atorvastatin; insulin resistance; branched-chain amino acid; protein phosphatase 2Cm; fibroblast growth factor 21; branched chain alpha-ketoate dehy-drogenase
- From: Chinese Pharmacological Bulletin 2025;41(7):1273-1282
- CountryChina
- Language:Chinese
- 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.
