The Mechanism Of Automatic Regulatory Loop Controlling The Expression Of Mitochondrial Derived Peptide MOTS-c In Skeletal Muscle

Objective: Type 2 diabetes is a chronic metabolic disease,which can be improved by exercise and diet intervention,and its main etiology is insulin resistance.The biological function of AMPK is related to sugar and fat metabolism.PGC-1? is closely related to diabetes,energy metabolism and obesity in the process of exercise.MO TS-c has the effect of improving insulin resistance and metabolic balance,and its effect is similar to exercise intervention.This study mainly reveals the upstream a nd downstream relationships among AMPK,PGC-1? and MOTS-c,and the internal relations of their interactions.Methods: This paper focuses on the study of C2C12 mouse myoblasts.The C2C12 cells were interfered by the application of MO TS-c,AMPK stimulants and inhibitors,the silencing and overexpression of PGC-1? gene.Western blot,q RT-PCR and ELISA were used to detect the expression of AMPK,PGC-1?,MOTS-c and ACC,and to observe their changes,so as to determine whether there is a pathway in this study and its role in improving the state of insulin resistance.Results: The expression of PGC-1? and MOTS-c changed with the change of AMPK;when AIC AR at the same concentration acted on C2C12 at different time,PGC-1? changed first compared with MO TS-c,and when Compound C at the same concentration acted on C2C12 at different time,PGC-1? and MOTS-c changed at the same time;the expression of each index protein in the Compound C group treated with MO TS-c was significantly increased compared with that in the C2C12 group treated with Compound C alone,while the expression of each index protein in the AICAR group treated with MOTS-c had no overlapping effect compared with that in the C2C12 group treated with AICAR alone,but it was still significantly increased compared with that in the control group;when PGC-1? was silenced,the expression of MOTS-c decreased significantly.After PGC-1? was silenced,the expression of MOTS-c in combination with MOTS-c intervention group was significantly higher than the group of PGC-1? silenced alone,but it decreased significantly compared with the group of MOTS-c intervention alone;when overexpression of PGC-1?,the expression of MOTS-c was significantly increased.After overexpression of PGC-1?,the expression of MOTS-c in combination with Compound C intervention group was significantly lower than that in overexpression of PGC-1? alone,and significantly higher than that in Compound C alone.Conclusion: The pathway of AMPK-PGC-1?-MOTS-c is existent;It is preliminarily determined that PGC-1? is the upstream regulator of MOTS-c;AMPK regulates the expression of MOTS-c through PGC-1?.