Peeyush Kumar T, Gireesh G, Jobin Mathew, Paulose C S
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin - 682 022, Kerala, India.
Life Sci. 2009 Nov 4;85(19-20):704-10. doi: 10.1016/j.lfs.2009.09.012. Epub 2009 Oct 3.
Chronic hyperglycaemia in diabetes involves a direct neuronal damage caused by intracellular glucose which leads to altered neurotransmitter functions and reduced motor activity. The present study investigated the effect of curcumin in the functional regulation of muscarinic and alpha7 nicotinic acetylcholine receptors, insulin receptors, acetylcholine esterase and Glut3 in the cerebellum of streptozotocin (STZ)-induced diabetic rats.
All studies were done in the cerebellum of male Wistar rats. Radioreceptor binding assays were done for total muscarinic, M(1) and M(3) receptors using specific ligands, and the gene expression was also studied using specific probes.
Our results showed an increased gene expression of acetylcholine esterase, Glut3, muscarinic M1, M3, alpha7 nicotinic acetylcholine and insulin receptors in the cerebellum of diabetic rats in comparison to control. Scatchard analysis of total muscarinic, M1 and M3 receptors showed an increased binding parameter, B(max) in diabetic rats compared to control. Curcumin and insulin inhibited diabetes-induced elevation in the gene expression of acetylcholine esterase, Glut3, insulin and cholinergic receptors in the cerebellum of diabetic rats.
Our studies suggest that curcumin plays a vital role in regulating the activity of cholinergic and insulin receptors and mechanism of glucose transportation through Glut3, which results in normalizing the diabetes-mediated cerebellar disorders. Thus, curcumin has a significant role in a therapeutic application for the prevention or progression of diabetic complications in the cerebellum.
糖尿病中的慢性高血糖涉及细胞内葡萄糖引起的直接神经元损伤,这会导致神经递质功能改变和运动活性降低。本研究调查了姜黄素对链脲佐菌素(STZ)诱导的糖尿病大鼠小脑中毒蕈碱型和α7烟碱型乙酰胆碱受体、胰岛素受体、乙酰胆碱酯酶和葡萄糖转运蛋白3(Glut3)功能调节的影响。
所有研究均在雄性Wistar大鼠的小脑中进行。使用特异性配体对总毒蕈碱型、M(1)和M(3)受体进行放射受体结合测定,并使用特异性探针研究基因表达。
我们的结果显示,与对照组相比,糖尿病大鼠小脑中乙酰胆碱酯酶、Glut3、毒蕈碱型M1、M3、α7烟碱型乙酰胆碱和胰岛素受体的基因表达增加。对总毒蕈碱型、M1和M3受体的Scatchard分析显示,与对照组相比,糖尿病大鼠的结合参数B(max)增加。姜黄素和胰岛素抑制糖尿病诱导的糖尿病大鼠小脑中乙酰胆碱酯酶、Glut3、胰岛素和胆碱能受体基因表达的升高。
我们的研究表明,姜黄素在调节胆碱能和胰岛素受体的活性以及通过Glut进行葡萄糖转运的机制中起着至关重要的作用,这导致糖尿病介导的小脑疾病正常化。因此,姜黄素在预防或延缓小脑糖尿病并发症的治疗应用中具有重要作用。