METHODS: Four-week-old female db/db mice were assigned to the kobusone (25 mg/kg body weight, intraperitoneally twice a day) or control group (same volume of PBS). Glucose levels and body weight were measured twice a week. After 6 weeks, intraperitoneal glucose tolerance tests and immunohistochemical studies were performed, and insulin levels were determined. The expression of mRNAs involved in cell proliferation, such as PI3K, Akt, cyclin D3 and p57Kip2, was measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR).
RESULTS: Kobusone reduced blood glucose levels after 3 weeks and more strongly increased serum insulin levels than the vehicle. Immunohistochemistry illustrated that kobusone increased 5-bromo-2\'-deoxyuridine incorporation into islet β-cells, suggesting that it can stimulate islet β-cell replication in vivo. RT-qPCR indicated that kobusone upregulated the mRNA expression of PI3K, Akt, and cyclin D3 and downregulated that of p57Kip2.
CONCLUSIONS: Our findings suggest that kobusone is a potent pancreatic islet β-cell inducer that has the potential to be developed as an anti-diabetic agent.
方法:将四周大的雌性db/db小鼠分配给kobusone(25mg/kg体重,每天两次腹膜内)或对照组(相同体积的PBS)。每周两次测量葡萄糖水平和体重。6周后,进行了腹膜内葡萄糖耐量试验和免疫组织化学研究,并测定胰岛素水平。参与细胞增殖的mRNA的表达,例如PI3K,Akt,通过定量逆转录聚合酶链反应(RT-qPCR)测量细胞周期蛋白D3和p57Kip2。
结果:与溶媒相比,Kobusone降低了3周后的血糖水平,并更强烈地增加了血清胰岛素水平。免疫组织化学显示,kobusone增加5-溴-2'-脱氧尿苷掺入胰岛β细胞,表明它可以在体内刺激胰岛β细胞复制。RT-qPCR表明,kobusone上调PI3K的mRNA表达,Akt,和细胞周期蛋白D3,并下调p57Kip2的表达。
结论:我们的研究结果表明,kobusone是一种有效的胰岛β细胞诱导剂,具有开发作为抗糖尿病药物的潜力。