| Objective:Base on the metabolomics method of 1H NMR (nuclear magnetic resonance), we will set up urinary metabolic fingerprint of insulin resistance rats, discove endogenous metabolites associated with IR, search related biomarkers and explore the molecular pathology mechanisms of metabolite levels of IR.We also focus on the correlation between biomarkers and skeletal muscle mitochondria metabolism, to figer out the metabolic pathways which related to exercise intervention of IR, and comprehensive analysis mitochondrial mechanism which related to exercise interventions of IR, to provide the latest theoretical and practical reference for the exercise against IR.Methods:We Select 30 2-month-old Wistar rats, randomly divided into normal group(normal diet:fat, protein, carbohydrate, the calorie content were 10%,21%,69%, n=20)and model group (high-fat diet:fat, protein, carbohydrate, the calorie content were 59%,20%,21%, n=20) after one-week adaptive feeding.Both groups were reared five weeks.The successful modeling of IR rats were randomly divided into quiet groups(IR) and exercise (IR+E) group(10 in each group). After 7 days adaptive wheel training, IRrats begin wheel exercise at the second level of Bedford5 times a week for six weeks exercise.Test the Insulin sensitivity with the labor-intensive hyperinsulinemic clamp technique and collect relevant assays animal samples after exercise.Results:1.Results of labor-intensive hyperinsulinemic clamp technique showed, normal group60-120minutes glucose infusion rate(GIR) is 12.78±2.06mg/(kg·min) and the model group is 6.51±1.71mg/(kg·min) which is significantly differentially.After exercise, normal group without exercise (N)GIR is 14.86±1.56mg/(kg·min), normal group with exercise(Ne) is 14.23±3.94mg/(kg·min), model group without exercise(IR) is 6.61± 1.79mg/(kg·min), model group with exercise(IRe) is 10.1±1.62mg /(kg·min).There are significant differences between IRgroup and IRegroup,IRgroup and N group, IRe group and N group.2.We got results according to the statistical analysis of the rat urine metabolite. we obtained 22 kinds of potential biomarkers significantly differentially.High-fat diet have a significantly influence on potential biomarkers which include? -ketoglutarate, Citrate, Taurine, Lysine, Hippurate, Creatine, Succinate, Asparagine, Sarcosine, Alanine, Lactate, Choline, Citrulline, Phenylalanine, Glycine, 2-aminoadipic acid.Exercise have a significantly influence on potential biomarkers which include?-ketoglutarate, Taurine, Hippurate, Sarcosine, Alanine, Lactate, Citrulline.Interaction have a significantly influence onpotential biomarkers which include ?-ketoglutarate, Citrate, Taurine, Lysine, Aspartic acid, Hippurate, Creatine, Succinate, Asparagine, Sarcosine, ?-alanine, Lactate, Choline, Citrulline, Trigonelline, Glycine, Phenylalanine, Threonine, Tryptophan, Glycine,2-aminoadipic acid, Argininosuccinate. 3.Detection of skeletal muscle mitochondrial function display that IR groupskeletal muscle mitochondrial protein concentration is 0.23± 0.07mg/ml, IRe group is 0.34±0.09mg/ml, Nis0.47±0.21mg/ml, Negroup is 0.67±0.30mg/ml.There are significant differences between IR and IRe, IR and N.IR groupskeletal muscle mitochondrial ATP concentration is 0.125± 0.020nmol/mg, IRegroup is0.186±0.028nmol/mg, Ngroup is 0.307± 0.008nmol/mg, Negroup is 0.500±0.070nmol/mg.There are significant differences between IRgroup and IRegroup, IRgroup and N group, IRe group and N group, Ne and N.Conclusion:By feeding high-fat diet, insulin resistance in rats modeling success. After six week exercise, the symptoms of insulin resistance model rats improved.Significantly different biomarkers most participate in energy metabolism, which suggest that insulin resistance may result from energy metabolism disorders, ?-ketoglutarate, Citrate, Taurine, Lysine play a important role in improving IR.Significantly different biomarkers get inproved which participate in Krebs cycle, rat skeletal muscle mitochondrial function were significantly improved.Thus suggest thatexercise may improve mitochondrial function to achieve the treatment of insulin resistance. |
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