College of Korean Medicine, Gachon University, Seongnam 13120, Korea.
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Molecules. 2021 Oct 28;26(21):6509. doi: 10.3390/molecules26216509.
The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic β-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced insulin secretion in response to high glucose levels with no toxic effects on INS-1 cells. The effect of schisandrin C was superior to that of gliclazide (positive control), a drug commonly used to treat type 2 diabetes (T2D). In addition, western blot analysis showed that the expression of associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), phosphatidylinositol 3-kinase (PI3K), Akt, and insulin receptor substrate-2 (IRS-2), was increased in INS-1 cells after treatment with schisandrin C. In addition, insulin secretion effect of schisandrin C were enhanced by the Bay K 8644 (L-type Ca channel agonist) and glibenclamide (K channel blocker), were abolished by the nifedipine (L-type Ca channel blocker) and diazoxide (K channel activator). Moreover, schisandrin C enhanced glucose uptake with no toxic effects on C2C12 cells. Western blot analysis showed that the expression of associated proteins, including insulin receptor substrate-1 (IRS-1), AMP-activated protein kinase (AMPK), PI3K, Akt, glucose transporter type 4 (GLUT-4), was increased in C2C12 cells after treatment with schisandrin C. Schisandrin C may improve hyperglycemia by enhancing insulin secretion in pancreatic β-cells and improving glucose uptake into skeletal muscle cells. Our findings may provide evidence that schisandrin C may be beneficial in devising novel anti-T2D strategies.
本研究旨在探讨三种木脂素（五味子醇 A、五味子醇 B 和五味子丙素）对大鼠 INS-1 胰岛β细胞胰岛素分泌和小鼠 C2C12 骨骼肌细胞葡萄糖摄取的影响。五味子醇 A 和五味子丙素可增强高糖环境下的胰岛素分泌，且对 INS-1 细胞无毒性作用。五味子丙素的作用优于格列齐特（阳性对照物，一种常用于治疗 2 型糖尿病（T2D）的药物）。此外，Western blot 分析表明，经五味子丙素处理后，INS-1 细胞中与胰岛素分泌相关的蛋白，包括过氧化物酶体增殖物激活受体 γ（PPARγ）、胰腺十二指肠同源盒 1（PDX-1）、磷酸肌醇 3-激酶（PI3K）、Akt 和胰岛素受体底物-2（IRS-2）的表达增加。此外，Bay K 8644（L 型钙通道激动剂）和格列本脲（K 通道阻滞剂）增强了五味子丙素的胰岛素分泌作用，而硝苯地平（L 型钙通道阻滞剂）和二氮嗪（K 通道激活剂）则消除了这种作用。此外，五味子丙素可增强葡萄糖摄取，且对 C2C12 细胞无毒性作用。Western blot 分析表明，经五味子丙素处理后，C2C12 细胞中与胰岛素分泌相关的蛋白，包括胰岛素受体底物-1（IRS-1）、AMP 激活的蛋白激酶（AMPK）、PI3K、Akt、葡萄糖转运蛋白 4（GLUT-4）的表达增加。五味子丙素可能通过增强胰岛β细胞胰岛素分泌和改善骨骼肌细胞葡萄糖摄取来改善高血糖。我们的研究结果为五味子丙素可能有助于制定新型抗 2 型糖尿病策略提供了证据。
