Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, China.
Experiment Education Center for Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
J Ethnopharmacol. 2015 May 26;166:168-75. doi: 10.1016/j.jep.2015.03.014. Epub 2015 Mar 17.
The radix of Acorus calamus L. (AC) is widely used in diabetes therapies in traditional folk medicine from America and Indonesia, and we have previously reported that the ethyl acetate fraction of AC (ACE) acts as an antidiabetic through insulin sensitizing, insulin releasing and alpha-glucosidase inhibitory activities. The present study is designed to investigate the effects and molecular mechanisms of ACE on glucagon-like peptide-1 (GLP-1) expression and secretion related to its hypoglycemic effects.
The hypoglycemic effect of ACE (100mg/kg, i.g.) was confirmed by testing blood glucose levels or via oral glucose tolerance test (OGTT) in streptozotocin (STZ) induced hyperglycemic mice, db/db diabetic mice and diet-induced obese (DIO) mice. Plasma insulin, GLP-1 levels and intestinal GLP-1 related gene expression were determined in STZ-induced and db/db diabetic mice. The in vitro effects of ACE (12.5μg/ml) on the expression and secretion of GLP-1 were detected in NCI-H716 intestinal L-cells, and the correlation between ACE and molecules in the Wnt signaling pathway was further explored.
ACE (100mg/kg) significantly lowered fasting blood glucose in STZ-induced and db/db diabetic mice and improved the OGTT in DIO mice. Insulin releasing and islet protective effects, along with the increased secretion of GLP-1, were observed. The expression of proglucagon gene (gcg) and post-translational processing gene prohormone convertase 3 (pc3) and the GLP-1 content in the culture medium of L-cells notably increased after the ACE treatment (12.5μg/ml). At the same time, β-catenin nuclear translocation occurred, and its downstream protein cyclin D1 was activated, showing the involvement of Wnt signaling.
ACE might activate Wnt signaling to increase the gene expression of gcg and pc3 and exert incretin effects, including insulinotropic and islet protection, to lower blood glucose levels via elevated GLP-1 secretion either directly or indirectly.
菖蒲根茎（AC）广泛应用于美国和印度尼西亚传统民间医学中的糖尿病治疗，我们之前报道过 AC 的乙酸乙酯部分（ACE）通过胰岛素增敏、胰岛素释放和α-葡萄糖苷酶抑制活性发挥抗糖尿病作用。本研究旨在探讨 ACE 对胰高血糖素样肽-1（GLP-1）表达和分泌的影响及其与降血糖作用的分子机制。
通过检测血糖水平或通过链脲佐菌素（STZ）诱导的高血糖小鼠、db/db 糖尿病小鼠和饮食诱导肥胖（DIO）小鼠的口服葡萄糖耐量试验（OGTT），证实 ACE（100mg/kg，ig）的降血糖作用。测定 STZ 诱导和 db/db 糖尿病小鼠的血浆胰岛素、GLP-1 水平和肠 GLP-1 相关基因表达。检测 ACE（12.5μg/ml）对 NCI-H716 肠 L 细胞 GLP-1 表达和分泌的体外作用，并进一步探讨 ACE 与 Wnt 信号通路中分子的相关性。
ACE（100mg/kg）显著降低 STZ 诱导和 db/db 糖尿病小鼠的空腹血糖，改善 DIO 小鼠的 OGTT。观察到胰岛素释放和胰岛保护作用，以及 GLP-1 的增加分泌。ACE 处理（12.5μg/ml）后，L 细胞中 proglucagon 基因（gcg）和翻译后加工基因 prohormone convertase 3（pc3）的表达以及培养基中的 GLP-1 含量明显增加。同时，β-连环蛋白核易位，其下游蛋白 cyclin D1 被激活，表明 Wnt 信号通路的参与。
ACE 可能通过激活 Wnt 信号增加 gcg 和 pc3 的基因表达，通过增加 GLP-1 分泌发挥肠促胰岛素作用，包括胰岛素增敏和胰岛保护，从而降低血糖水平，无论是直接还是间接。
