科研之友
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摘要
The prevalence of type-2 diabetes is rapidly increasing. Currently, exenatide is the first medicine which mimics incretin. However, it requires subcutaneous injection twice a day, an inconvenient way for patients. In this study, we identified a novel peptide with similar pharmacology to exenatide in rodents as GLP-1 receptor agonist which consists of 17 amino acids (17P). It promotes Ins-1 cell proliferation and insulin secretion and lowers blood glucose of diabetic rats. 17P was synthetized by solid-phase peptide synthesis. Interactions between GLP-1 receptor and 17P were studied by Bio-layer interferometry. Ins-1 cell proliferation was studied by MTT assay. ELISA was used to study Ins-1 cell insulin secretion. In vivo tests were performed with male Wistar rats. We used high fat diet and STZ injection to induce a type-2 diabetic rats model. Then, those rats were randomized to different test groups, and administered exenatide, 17P and saline water injection, to evaluate different responses. Based on HPLC (high performance liquid chromatography) and MS (mass spectrometry), 17P synthesis was successful. Bio-layer interferometry data showed a close interaction between GLP-1 receptor and 17P. 17P treatment of Ins-1 cells for 24 h could promote cell proliferation and insulin secretion in a dose-dependent manner. Administration of 17P in HF-STZ male Wistar rats demonstrated that 17P could lower the level of blood glucose and stabilize the body weight of the diabetic rats. All 17P treatments were similar to treatment with exenatide. In vitro and in vivo studies demonstrated that 17P could relieve symptoms of type-2 diabetes. Therefore, 17P could be developed as a promising type-2 diabetes therapeutic drug.
- 出版日期2018-6
- 单位吉林大学
