Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Technology and Business University, Chongqing, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):787-91. doi: 10.1093/abbs/gmt069. Epub 2013 Jun 26.
Although cognitive dysfunction in diabetic patients has been explored extensively, diabetic complications of the central nervous system have not been studied. We have reported previously that geniposide has neurotrophic and neuroprotective activities with the activation of glucagons-like peptide 1 receptor, and regulates glucose-stimulated insulin secretion in vitro. But the role of geniposide on diabetic complications, especially on the neurodegenerative diseases, remains to be investigated. In this study, we investigated the effect of geniposide on the level of Aβ1-42 in the hippocampi of streptozotocin-induced diabetic rats and explored its possible mechanism. The results demonstrated that, accompanied with the improvement of insulin and blood glucose, treatment with geniposide decreased the Aβ1-42 level and improved the expression of insulin-degrading enzyme, which is the key degrading enzyme of Aβ peptide. The results of present study will help to understand the biochemical mechanisms of neuronal dysfunction and death in diabetes and to develop an efficient therapeutic strategy on Alzheimer's disease.
尽管糖尿病患者的认知功能障碍已经得到了广泛的研究,但中枢神经系统的糖尿病并发症尚未得到研究。我们之前曾报道过,栀子苷通过激活胰高血糖素样肽 1 受体具有神经营养和神经保护作用,并调节体外葡萄糖刺激的胰岛素分泌。但是栀子苷在糖尿病并发症中的作用,特别是在神经退行性疾病中的作用,仍有待研究。在这项研究中,我们研究了栀子苷对链脲佐菌素诱导的糖尿病大鼠海马中 Aβ1-42 水平的影响,并探讨了其可能的机制。结果表明,随着胰岛素和血糖的改善,栀子苷治疗降低了 Aβ1-42 水平并改善了胰岛素降解酶的表达,胰岛素降解酶是 Aβ 肽的关键降解酶。本研究的结果将有助于了解糖尿病中神经元功能障碍和死亡的生化机制,并为阿尔茨海默病开发有效的治疗策略。