| It is well known that diabetes is a chronic metabolic disease. As study deepen,diabetes was classified into two types (T1DM) and (T2DW) by different dependen.Diabetes mainly characterized by hyperglycemia together with other pathological,and the rate of which was increasing. Compared with T1DW, T2DW had a higherrisk, and the rate was over90%. The main symptoms of T2DW were high bloodsugar, drink much more feed with angularPolydipsia eatEat polydipsia, insulin resistance, beta cell dysfunction caused by insulinsecretion insufficient. It was considered that the pathogenicity of T2WD was notonly a single factor, but also genetic and environmental factors. Due to the ordinaryand multiple of T2WD， the mortality rate remained at a high level。The formation of T2WD was various。 External factors included populationaging，diet and lifestyle disorders，reduction of exercise， obesity increasing causedby high fat food intake and so on. The appearance and fast growth of children andteenager diabetes patients caused by over obesity was another cannot be ignoredreason。In addition to the external factors，internal factors were also closely relatedwith T2WD such as individual genetic factors which included PPARG, JAZF1, ATP,WFS1and so on, in which ATP is sensitive transcription factors in islet and mainlycontrol glucagon gene and glucagon peptide1(glp-1) expression.Glp-1receptor was one kind of G protein coupled receptors and played animportant role in the process of glucose metabolism. Previous study have reportedthat the activity of GLP－1was significant low in T2WD patients which influencethe secretion of insulin。 Since the sequence of Glp-1was too long， the cost ofsynthesis and purification is much higher. Therefore, study on glp-1short peptidewas important for researching and treatment of T2DW。 Nowadays glp-1receptor has been widely used as a target in screening of diabetes drugs.This paper aims to found a high activity GLP－1analogues through screening glp-1receptors。 Our study firstly expressed the N side extracellular domain byprokaryotic expression and then we used phage peptide library screening technologyto screen peptide with high affinity to glp-1receptors，namely glp-1analog peptides.Secondly, glp-1analog peptides were synthesized and characterized. Thirdly, acellular experiment was performed to examine the glp-1analog peptides bioactivityon islet beta cell proliferation and the insulin secretion capacity. Finally, we studiedthe glp-1analog peptides activity in vivo。The rat blood glucose levels， insulinlevels and serum biochemical indexes were detected to evaluate simulation peptideeffect on type2diabetic rats. Besides，we hope our study provided importantexperience for T2DW basis research and clinical treatment. |
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