Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats: Antagonism by pyridoxine and insulin
Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats: Antagonism by pyridoxine and insulin
复制标题
DOI：
10.1016/j.neulet.2010.07.042
复制
发表时间：
2010-10-08
影响因子：
2.5
通讯作者：
Paulose, C. S.
中科院分区：
文献类型：
--
作者：
Abraham, Pretty Mary;Anju, T. R.;Paulose, C. S.
胰岛素分泌和葡萄糖稳态是通过β-肾上腺素能功能来实现的。吡哆醇参与5-羟色胺合成中的脱羧步骤。本研究观察了胰岛素和吡哆醇联合应用对链脲佐菌素诱导的糖尿病大鼠大脑皮质和脑干5-HT和5-HIAA含量、5-HT受体结合、5-HTT基因表达及免疫组织化学的影响。糖尿病大鼠大脑皮质和脑干5-HT含量显著降低（P < 0.01），5-HIAA含量显著升高（P < 0.001）。与对照组相比，糖尿病大鼠大脑皮层5-HT受体结合参数B-max和K-d显著降低（p < 0.001），而脑干5-HT受体结合参数B-max和K-d显著升高（p < 0.001）。与对照组相比，糖尿病大鼠大脑皮层中5-HTT的基因表达研究显示出显著下调（p < 0.001），脑干中5-HTT的基因表达研究显示出显著上调（p < 0.001）。免疫组化结果显示，胰岛素和吡哆醇治疗可使糖尿病大鼠大脑皮质和脑干中5-HT含量、B-max、K-d和5-HTT基因表达逆转至接近对照组水平。因此，我们的研究结果表明，吡哆醇沿着胰岛素具有调节胰岛素合成和释放的作用，通过β-肾上腺素能功能，这在糖尿病的管理中具有临床意义。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Insulin secretion and glucose homeostasis is implicated through serotonergic function. Pyridoxine is involved in decarboxylation step in synthesis of serotonin. The present study was carried out to find the role of insulin in combination with pyridoxine on the concentrations of 5-HT and 5-HIAA, 5-HT receptor binding, 5-HTT gene expression and immunohistochemistry studies in the cerebral cortex and brainstem of streptozotocin induced diabetic rats. 5-HT content showed a significant decrease with a significant increase in 5-HIAA in cerebral cortex (p < 0.01) and brain stem (p < 0.001) in diabetic rats. 5-HT receptor binding parameters, B-max and K-d, showed a significant decrease (p < 0.001) in diabetic rats in cerebral cortex whereas in brainstem it showed a significant increase (p < 0.001) compared to control. Gene expression studies of 5-HTT in cerebral cortex showed a significant down regulation (p < 0.001) and in brainstem an upregulation (p < 0.001) in diabetic rats compared to control. Insulin and pyridoxine treatment to diabetic rats reversed the 5-HT content, B-max, K-d and gene expression of 5-HTT confirmed by immunohistochemistry studies in cerebral cortex and brainstem to near control. Thus our results suggest that pyridoxine along with insulin has a role in the regulation of insulin synthesis and release through serotonergic function which has clinical significance in the management of diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.