Activation of islet 5-HT₄ receptor regulates glycemic control through promoting insulin secretion

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• 作者：Hui Chen ^{chenhui0429@163.com" class="auth_mail" title="E-mail the corresponding author} ; Feng Hong ^{hongfengshengli@163.com" class="auth_mail" title="E-mail the corresponding author} ; Ye Chen ^{5117149cy@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Ji Li ^{0925liji@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Yuan-Sheng Yao ^{hylyyys@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yue Zhang ^{rebecca@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Li-Fei Zheng ^{13581582937@163.com" class="auth_mail" title="E-mail the corresponding author} ; Jin-Xia Zhu ; ^{zhu_jx@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：5-HT ; 5-hydroxytryptamine ; INS ; insulin ; GLU ; glucagon ; PP ; pancreatic polypeptide ; SST ; somatostatin
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：789
• 期：Complete
• 页码：354-361
• 全文大小：6240 K

文摘

Mosapride, a gastrointestinal prokinetic drug, is an agonist of 5-hydroxytryptamine (5-HT) receptor 4 that also reduces blood glucose. Whether 5-HT₄ receptor is distributed in pancreatic islets and whether mosapride can directly stimulate insulin secretion is unclear. In the present study, the protein expression and cellular location of 5-HT₄ receptor in pancreas was detected through western blotting and immunofluorescence. The acute effects of 5-HT₄ receptor agonists, mosapride and prucalopride, on insulin secretion were investigated in vivo and in vitro in normal and alloxan-induced diabetes rats. The results indicated that 5-HT₄ receptor immunoreactivity was co-existed in the islets insulin-immunoreactive cells of rat, mouse, pig and human. However the immunoreactive cells of insulin and 5-HT₄ receptor and the protein expression of 5-HT₄ receptor were significantly decreased in the pancreas of alloxan-induced diabetes rats. In normal rats, mosapride and prucalopride decreased blood glucose and increased insulin secretion during glucose tolerance test, in association with an increase in glucose-stimulated insulin secretion, which was abolished by the 5-HT₄ receptor antagonist GR113808. In diabetes rats, mosapride and prucalopride failed to improve blood glucose and insulin levels in the group of 180 mg/kg alloxan, but increased glucose-stimulated insulin secretion in the group of 120 mg/kg alloxan in vitro. We conclude that 5-HT₄ receptor is distributed in the islet β cell. Activation of 5-HT₄ receptor is able to stimulate insulin secretion directly, thereby reduce blood glucose. The study provides important experimental evidences for the 5-HT₄ receptor regulating insulin secretion and acting as a potential drug target in diabetes treatment.