Novel Cyclic Peptide COX_52-69 Enhances Insulin Sensitivity

With the improvement of people’s living standards,more and more people have decreased insulin receptor sensitivity,which leads to various diseases such as hypertension,obesity,and diabetes.In previous experiments,a new short peptide COX_52-69 discovered in our laboratory was cyclized.Cir-COX_52-69 could reduce high glucose-induced insulin secretion and at the same time,it does not increase blood sugar,and even has a certain effect of lowering blood sugar.This phenomenon suggests that the body’s sensitivity to insulin has increased.In this study,Cir-COX_52-69 was indirectly verified from the glucose tolerance test（Oral Glucose Tolerance Test,OGTT）and insulin release assay to improve insulin receptor sensitivity.Experiments directly demonstrate this effect of Cir-COX_52-69.In the hyperinsulinemic-euglycemic clamp experiment,the glucose infusion rate after administration was significantly increased to 3.9 times that before administration（P<0.001）.This shows that the cyclic peptide COX increases the body’s sensitivity to insulin.In order to reveal the molecular mechanism by which this peptide increases the body’s sensitivity to insulin,by choosing an insulin receptor blocker,BMS-754807 into rats,it was found that the phenomenon of blood glucose drop caused by Cir-COX_52-69 was inhibited,this suggests that the mechanism of increased sensitivity is inseparable from the insulin receptor（Insulin receptor,InsR）.and finally selected InsR gene for verification.The SPF grade male SD rats were divided into two groups.The experimental group was intragastrically administered with cyclopeptide and 20 % glucose,while the control group was intragastrically administered with the same volume of cyclopeptide-dissolving solvent and 20 % glucose,and the insulin receptor（InsR）levels were detected.mRNA level and protein level.InsR were determined by real-time fluorescence quantitative technology and Western blotting technology,and it was found that their expression levels were significantly up-regulated after rats were given CirCOX_52-69,whether at the mRNA level or the protein level.Clinically,glucagon is used to improve the hypoglycemia caused by hyperinsulinemia.However,while increasing blood sugar,this method makes the amount of insulin in the body secreted under stress,which further aggravates hyperinsulinemia but lowers blood sugar.At present,there is a lack of a drug that can break the vicious cycle of excessive insulin secretion and insulin resistance in hyperinsulinemia and obesity.Cir-COX_52-69 itself,as a polypeptide,has high specificity,affinity,With low side effects,it also has the advantage of being orally available.While maintaining the function of the short peptide COX_52-69 to reduce glucose-induced insulin secretion,it also has the effect of greatly enhancing insulin sensitivity.Therefore,it is promising for the treatment of diseases related to insulin resistance in the future.