Characterization of an insulinotropic peptide from skin secretions of Odorrana andersonii
Characterization of an insulinotropic peptide from skin secretions of Odorrana andersonii
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DOI：
10.1002/psc.3017
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发表时间：
2017-06
影响因子：
2.1
通讯作者：
Wei-Jie Shang;Xinwang Yang;Xiaoman Ju;Y. Xie;Yun Zhang;Wen-Hui Lee
中科院分区：
文献类型：
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作者：
Wei-Jie Shang;Xinwang Yang;Xiaoman Ju;Y. Xie;Yun Zhang;Wen-Hui Lee
促胰岛素肽药物被认为是抗糖尿病治疗的潜在候选药物。在本研究中，一种新的促胰岛素分泌肽，命名为OA‐A1，是从安氏臭蛙蛙皮肤分泌物中纯化的。成熟OA-A1被确定为1965.049 Da肽，氨基酸序列为LVGKLLKGAVGDVCGLLPIC，其中分子内二硫键由两个半胱氨酸残基形成。在细胞水平，OA-A1对小鼠来源的胰腺β-TC-6细胞表现出有效的增殖促进作用，并在最低浓度为1 nM时显著刺激β-TC-6细胞中的胰岛素释放。在动物模型中，OA‐A1在小鼠中也显示出剂量依赖性胰岛素释放作用。在1 nmol/kg至1 μmol/kg的浓度范围内，OA-A1对链脲佐菌素（STZ）诱导的糖尿病小鼠具有显著的急性降血糖作用。与生理盐水对照组相比，OA-A1治疗21天后（1-100 nmol/kg），糖尿病小鼠的胰岛面积呈剂量依赖性增加。此外，OA-A1显著改善STZ诱导的糖尿病小鼠的口服葡萄糖耐量。总之，这些结果表明，OA-A1为开发新型抗糖尿病治疗药物提供了一个很好的模板。Copyright © 2017 European Peptide Society and John Wiley & Sons，Ltd.
Insulinotropic peptide agents are regarded as potential candidates for anti‐diabetic treatment. In the present study, a novel insulinotropic peptide, termed OA‐A1, was purified from frog skin secretions of Odorrana andersonii. Mature OA‐A1 was determined to be a 1965.049 Da peptide with an amino acid sequence of LVGKLLKGAVGDVCGLLPIC, in which an intramolecular disulfide bridge was formed by two cysteine residues. At the cellular level, OA‐A1 exhibited potent proliferation promoting effects on mouse‐derived pancreatic β‐TC‐6 cells and significantly stimulated insulin release in β‐TC‐6 cells at a minimum concentration of 1 nM. In the animal model, OA‐A1 also showed a dose‐dependent insulin‐releasing role in mice. At concentrations ranging from 1 nmol/kg to 1 μmol/kg, OA‐A1 had a significant acute hypoglycemic effect on streptozotocin (STZ)‐induced diabetic mice. The pancreatic islet areas of diabetic mice increased dose‐dependently after 21 days of OA‐A1 treatment (1–100 nmol/kg) compared with those of the saline control group. Moreover, OA‐A1 significantly improved the oral glucose tolerance of STZ‐induced diabetic mice. Taken together, these results suggest that OA‐A1 provides an excellent template for the development of novel anti‐diabetic therapeutic agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.