Cell Biology-Cardio Vascular Unit, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, P.O. BOX 3354, Riyadh 11211, Saudi Arabia.
Neurochem Res. 2011 Nov;36(11):2116-26. doi: 10.1007/s11064-011-0536-9. Epub 2011 Jun 26.
Complications arising from diabetes mellitus include cognitive deficits, neurophysiological and structural changes in the brain. The current study investigated the expression of cholinergic, insulin, Vitamin D receptor and GLUT 3 in the brainstem of streptozotocin-induced diabetic rats. Radioreceptor binding assays and gene expression were done in the brainstem of male Wistar rats. Our results showed that B(max) of total muscarinic, muscarinic M3 receptors was increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. A significant increase in gene expression of muscarinic M3, α7 nicotinic acetylcholine, insulin, Vitamin D₃ receptors, acetylcholine esterase, choline acetyl transferase and GLUT 3 were observed in the brainstem of diabetic rats. Immunohistochemistry studies of muscarinic M1, M3 and α7 nicotinic acetylcholine receptors confirmed the gene expression at protein level. Vitamin D₃ and insulin treatment reversed diabetes-induced alterations to near control. This study provides an evidence that diabetes can alter the expression of cholinergic, insulin, Vitamin D receptors and GLUT 3 in brainstem. We found that Vitamin D₃ treatment could modulate the Vitamin D receptors and plays a pivotal role in maintaining the glucose transport and expressional level of cholinergic receptors in the brainstem of diabetic rats. Thus, our results suggest a therapeutic role of Vitamin D₃ in managing neurological disorders associated with diabetes.
糖尿病引起的并发症包括认知障碍、神经生理和大脑结构变化。本研究探讨了链脲佐菌素诱导的糖尿病大鼠脑干中胆碱能、胰岛素、维生素 D 受体和 GLUT3 的表达。在雄性 Wistar 大鼠的脑干中进行了放射受体结合测定和基因表达。我们的结果表明，与对照组相比，糖尿病大鼠的总毒蕈碱、毒蕈碱 M3 受体的 B(max)增加，毒蕈碱 M1 受体减少。糖尿病大鼠脑干中观察到毒蕈碱 M3、α7 烟碱型乙酰胆碱受体、胰岛素、维生素 D₃ 受体、乙酰胆碱酯酶、胆碱乙酰转移酶和 GLUT3 的基因表达显著增加。毒蕈碱 M1、M3 和α7 烟碱型乙酰胆碱受体的免疫组织化学研究证实了蛋白水平的基因表达。维生素 D₃ 和胰岛素治疗可使糖尿病引起的改变逆转至接近对照水平。这项研究提供了证据表明，糖尿病可以改变脑干中胆碱能、胰岛素、维生素 D 受体和 GLUT3 的表达。我们发现，维生素 D₃ 治疗可以调节维生素 D 受体，并在维持糖尿病大鼠脑干中葡萄糖转运和胆碱能受体表达水平方面发挥关键作用。因此，我们的结果表明维生素 D₃ 在治疗与糖尿病相关的神经紊乱方面具有治疗作用。
