6-shogaol Improves Age-related Insulin Resistance In Rats Skeletal Muscle

Purpose To investigate the effects and mechanisms of 6-shogaol improves age-related insulin resistance in rats skeletal muscle.Methods Twenty-five male SD rats?20 months old?were divided randomly into three groups:aged control group?Aged,n=9?,aged low-dose6-shogaol at 0.125 mg·kg^-1?SL,n=8?and aged high-dose 6-shogaol at 0.5mg·kg^-1?SH,n=8?.Six male SD rats?3 months old?were used as a young control group?Young,n=6?.At the end of week 7,enzymatical method was used for the examination of fasting plasma concentrations of glucose,triglyceride?TG?,total cholesterol?TC?and non-esterified fatty acid?NEFA?.Fasting plasma insulin level was determinated by Elisa method.The expression of total insulin receptor substrate-1?IRS-1?,phosphorylated IRS-1?Ser307?(p-IRS-1^Ser307),phosphatidylinositol 3-kinase?PI3K?,total protein kinase B?AKT?,phosphorylated AKT?Ser473?(p-AKT^Ser473),Adiponectin,H2AX,phosphorylated H2AX?Ser139?(p-H2AX^Ser139),Liver kinase B1?LKB1?,AMP-activated protein kinase?AMPK?,phosphorylated AMPK^Thr172(p-AMPK^Thr172),peroxisome proliferator activated-?coactivator-1??PGC-1??,cytochrome c oxidase subunit??COX??,sirtuin1?SIRT1?proteins in skeletal muscle of rats were analyzed by Western blot.The expression of Adiponectin,H2AX,DNA-dependent protein kinas?DNA-PK?,LKB1 and AMPK mRNAs in skeletal muscle of rats were determinated by Real-time PCR.Results 6-Shogaol(0.500 mg·kg^-1)remarkably attenuated higher fasting plasma concentrations of glucose,NEFA and insulin,homeostasis model of assessment for insulin resistence index?HOMA-IR?and adipose tissue insulin resistance index?Adipo-IR?in aged control group?P<0.01,P<0.05?.Ratios of glucose to insulin and NEFA to insulin were significantly increased by 6-shogaol(0.500 mg·kg^-1)treatment in comparison with the aged control group?P<0.01?.Compared with the aged control group,6-shogaol?0.500 mg·kg-1?notably decreased DNA-PK mRNA level?P<0.05?.Adiponectin,LKB1 and CS mRNAs level were markedly enhanced by 6-shogaol?0.500 mg·kg-1?treatment in comparison with the aged control group?P<0.05?.6-Shogaol(0.500 mg·kg^-1)evidently reduced superior ratios of p-IRS-1^Ser307/IRS-1 and p-H2AX^Ser139/H2AX in aged control group and pronouncedly advanced ratios of p-IRS-1^Tyr632/IRS-1,p-AKT^Ser473/AKT and p-AMPK^Thr172/AMPK and the expression of Adiponectin,LKB1,SIRT1,PGC-1?and COX?proteins in comparison with the aged control group?P<0.05?.Activities of T-SOD,SDH and NADH and ATP contents were significantly increased by 6-shogaol(0.500mg·kg^-1)treatment in comparison with the aged control group?P<0.05?.6-Shogaol(0.500 mg·kg^-1)obviously attenuated higher MDA content than the aged control group?P<0.05?.Conclusion 6-Shogaol can improve aging-related insulin resistance in skeletal muscle of rats by regulating pathways of IRS-1/PI3K/AKT and LKB1/AMPK/SIRT1/PGC-1?which was modulated via Adiponectin and DNA-PK.