中文摘要：

为了寻找能够模拟胰岛素生物活性的小肽,以胰岛素多克隆抗体为靶标,筛选噬菌体展示随机C7C环肽库.3轮筛选后,通过ELISA方法挑取与靶分子特异性结合的15个阳性克隆,测序获得两条序列,分析所得序列并合成相应短肽.通过细胞生物学活性检测,小肽CPTSQANSC（ZJ1）能够竞争性的抑制胰岛素与其受体的结合,并对正常小鼠和四氧嘧啶诱导的糖尿病小鼠,都有明显的降血糖作用.上述结果表明,小肽CPTSQANSC具有胰岛素样生物学活性.而小肽CVQPSHSSC（ZJ2）表现出胰岛素拮抗活性,能引起正常小鼠血糖升高.这表明筛选到了能够模拟胰岛素表位的短肽CPTSQANSC,可能为治疗胰岛素依赖性糖尿病提供了新线索.

英文摘要：

Diabetes mellitus is a chronic disease that is growing in prevalence worldwide, We used phage display to generate peptides that mimic the epitopes involved in protein-protein interaction between insulin and the insulin receptor. The polyclonal antibody of insulin was used to screen the peptide mimetic from phage C7C peptide library. After 3 rounds of screening, positive clones were selected by the methods of ELISA. Eventually 15 out of 20 eluted clones have been identified to bind to the anti-insulin antibody specifically, and the sequences of peptides were deduced by DNA sequencing. Based on competitive ELISA studies, the peptide CP＇PSQANSC has been identified to bind to a similar hotspot of the insulin receptor on the cell surface. The biological activity was measured by injecting i.v. the synthetic peptide into normal and alloxan-induced diabetic mice. The blood sugar was determined to evaluate the insulin-like function. The results showed that the peptide had insulin-like activity. However, the peptide CVQPSHSSC showed the antagonist effect and slightly increased the blood-sugar level in mice. In conclusion, the short peptide CPTSQANSC has glucoselowering effects, which may have potential clinical applications.