Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China; Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China.
Eur J Pharmacol. 2018 Jan 5;818:115-123. doi: 10.1016/j.ejphar.2017.10.033. Epub 2017 Oct 20.
Puerarin, a major active isoflavone extracted from the root of Pueraria lobate, significantly increases plasma β-endorphin and insulin levels and improves impaired insulin signaling in diabetic animals. However, the target tissues and underlying mechanisms in and through which puerarin functions to ameliorating insulin resistance remains largely unclear. In this study, we showed that puerarin enhanced μ-opioid receptor expression and phosphorylation, and increased insulin-stimulated glucose transporter 4 translocation to the plasma membrane in the skeletal muscle of diabetic rats, which were recaptured by a direct application of puerarin in the palmitate-induced insulin-resistant L6 myotubes. Naloxone, an antagonist of μ-opioid receptor, blocked these functions of puerarin. No β-endorphin was detected either in the muscle of diabetic rats or in the palmitate-induced insulin-resistant L6 cells. Furthermore, we presented the evidence to show the interaction between μ-opioid receptor and insulin receptor substrate 1 in the muscle tissues and cells. These results suggested that puerarin improved insulin sensitivity in the skeletal muscle at least in part by its local effects involving μ-opioid receptor function.
葛根素是从野葛的根部提取的主要活性异黄酮，它显著提高了血浆β-内啡肽和胰岛素水平，并改善了糖尿病动物的胰岛素信号转导受损。然而，葛根素在改善胰岛素抵抗方面的作用的靶组织和潜在机制在很大程度上仍不清楚。在这项研究中，我们表明，葛根素增强了μ-阿片受体的表达和磷酸化，并增加了胰岛素刺激的葡萄糖转运蛋白 4向糖尿病大鼠骨骼肌质膜的易位，这一作用被直接应用于棕榈酸诱导的胰岛素抵抗 L6 肌管中的葛根素所捕捉。纳洛酮，μ-阿片受体的拮抗剂，阻断了葛根素的这些作用。无论是在糖尿病大鼠的肌肉中还是在棕榈酸诱导的胰岛素抵抗的 L6 细胞中，都没有检测到β-内啡肽。此外，我们还提供了证据表明，μ-阿片受体和胰岛素受体底物 1 在肌肉组织和细胞中相互作用。这些结果表明，葛根素至少部分地通过其涉及μ-阿片受体功能的局部作用改善了骨骼肌的胰岛素敏感性。
