Study On The Exendin-4Short-peptide Analogue Design And Anti-diabetic Activities

In recent years,diabetes is becoming more and more worldwide,it hasbecome the third uncured disease except cancer and Cardiovascular andcerebrovascular diseases,and90percent of people get type2diabetes,sostudy for type2diabetes has become a research hot spot.Today,type2diabetes cannot be cured,but only be relieved by medicine oral-taken or insulininjected to steady the patients’ blood glucose.Some kinds of certain medicineshave been approved to be reacted including sulfonylureas、metformin、Thealpha-glucosidase inhibitor and GLP-1receptor agonist.Exendin-1belongsto GLP-1receptor agonist,it is a kind of polypeptide separated from SouthSheila Gila saliva which is consisted of39amino acids.Its homology withman’s GLP-1was up to53%.Exexdin-1acted like GLP-1,it could elevateinsulin transcriptional level in man’s body,stimulate insulin secretion,whereasto control man’s blood glucose level.However,the half-life period of GLP-1isshort,merely to be2min,the half-life period of Exendin-4is long to be9h，soas to be a promising medicine to cure diabetes in the future.However，the composition of Exendin-4is complicated and consist of39amino acids,present studies are focusing on how to optimize its structure,suchas how to shorten its peptide chain,and in the same time,not to shorten itshalf-life period.This paper mainly studied a kind of polypeptide which is consistof17amino acids,it was designed from two parts,the first one is from formerstudy in our lab,by the method of phage display peptide screening,we got12Pwhich is similar to Exendin-4and acted to stimulate INS-1cell proliferation andwas easy to affined GLP-1receptor,in another word, it is an analogue toExentin-4.And the second part is a pentapeptide which is a kind of GLP-1receptor agonist.Then we designd to combine this two sequences ofpolypeptide,we hoped and studied whether the new polypeptide17P could acted like Exentin-4,stimulate INS-1cell proliferation and bond to GLP-1receptor steadily.This paper approved17P could stimulate INS-1cell insulin secretion invitro,and down-regulate diabetic mice blood glucose and body weight invivo.After5week17P injection through oral glucose tolerance test,resultsshow after being cured by17P,diabetic mice could tolerate glucose andreaction of glucose downsizing is steady.In the study of17P stabilization,we found that it was not steady inserum,and had a short half-life period.However,it has less amino acids,shorterthan Exentin-4,whereas its activity of curing diabetes is promising and similarto Exendin-4.This makes it hot to be studied.Afterwards, we are going to focuson how to lengthen its half-life period,to make it be approved better.