The small molecule kobusone can stimulate islet β-cell replication in vivo

摘要

Objective To investigate the ability of kobusone to reduce high glucose levels and promote β-cell proliferation. 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 p57 ~(Kip) ~( 2 ), 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 p57 ~(Kip2). Conclusion 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.