Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung City, Taiwan, 90801.
Chief Secretary's Office, Chiayi Hospital, Ministry of Health and Welfare, Chiayi City, Taiwan, 60001.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Oct;390(10):997-1003. doi: 10.1007/s00210-017-1399-7. Epub 2017 Jul 8.
Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetics. Morin has been demonstrated to increase plasma insulin. However, the mechanism(s) remains unknown. The present study is designed to investigate the effect of morin on the imidazoline receptor (I-R) that regulates insulin secretion. We used Chinese hamster ovary (CHO) cells transfected with an I-R expression construct (NISCH-CHO-K1 cells) to identify the direct effect of morin on the I-R. Moreover, the imidazoline I receptor (I-3R) is known to be present in pancreatic β cells and involved in insulin secretion. Therefore, we applied a specific antagonist (KU14R) to block I-3R in diabetic rats. Additionally, the effect of morin on insulin secretion was characterized in isolated pancreatic islets. Morin decreased blood glucose levels by increasing plasma insulin levels in diabetic rats. In CHO cells expressing an I-R, morin increased calcium influx in a dose-dependent manner. Additionally, KU14R dose-dependently inhibited the morin-induced effects, including hypoglycemia and the increase in insulin secretion and plasma C-peptide levels, in diabetic rats. Furthermore, morin enhanced insulin secretion from isolated pancreatic islets, and this effect was also dose-dependently inhibited by KU14R. Phospholipase C (PLC) is known to couple with the I-R, and a PLC inhibitor dose-dependently attenuated the insulin secretion induced by morin in isolated pancreatic islets. Taken together, these data suggest that morin can activate I-3R to enhance insulin secretion. Therefore, it would be useful to develop morin into a treatment for diabetic disorders.
莫林是番石榴中含有的一种类黄酮，已知可降低糖尿病患者的高血糖。莫林已被证明能增加血浆胰岛素。然而，其机制尚不清楚。本研究旨在研究莫林对调节胰岛素分泌的咪唑啉受体（I-R）的影响。我们使用转染 I-R 表达构建体的中国仓鼠卵巢（CHO）细胞（NISCH-CHO-K1 细胞）来鉴定莫林对 I-R 的直接影响。此外，已知咪唑啉 I 受体（I-3R）存在于胰腺β细胞中，并参与胰岛素分泌。因此，我们应用特异性拮抗剂（KU14R）在糖尿病大鼠中阻断 I-3R。此外，我们还研究了莫林对分离的胰岛胰岛素分泌的影响。莫林通过增加糖尿病大鼠血浆胰岛素水平降低血糖水平。在表达 I-R 的 CHO 细胞中，莫林以剂量依赖的方式增加钙离子内流。此外，KU14R 剂量依赖性地抑制了莫林诱导的作用，包括低血糖和胰岛素分泌以及血浆 C 肽水平的增加，在糖尿病大鼠中。此外，莫林增强了分离的胰岛的胰岛素分泌，而 KU14R 也以剂量依赖的方式抑制了这种作用。已知磷脂酶 C（PLC）与 I-R 偶联，PLC 抑制剂剂量依赖性地减弱了莫林在分离的胰岛中诱导的胰岛素分泌。总之，这些数据表明，莫林可以激活 I-3R 来增强胰岛素分泌。因此，将莫林开发成治疗糖尿病的方法将是有用的。
