Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
Division of Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Eur J Pharmacol. 2015 Dec 5;768:207-16. doi: 10.1016/j.ejphar.2015.10.055. Epub 2015 Oct 31.
Skeletal muscle is the principal site for postprandial glucose utilization and augmenting the rate of glucose utilization in this tissue may help to control hyperglycemia associated with diabetes mellitus. Here, we explored the effect of Deoxyandrographolide (DeoAn) isolated from the Andrographis paniculata Nees on glucose utilization in skeletal muscle and investigated its antihyperglycemic effect in vivo in streptozotocin-induced diabetic rats and genetically diabetic db/db mice. In L6 myotubes, DeoAn dose-dependently stimulated glucose uptake by enhancing the translocation of glucose transporter 4 (GLUT4) to cell surface, without affecting the total cellular GLUT4 and GLUT1 content. These effects of DeoAn were additive to insulin. Further analysis revealed that DeoAn activated PI-3-K- and AMPK-dependent signaling pathways, account for the augmented glucose transport in L6 myotubes. Furthermore, DeoAn lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats and also suppressed the rises in the fasting blood glucose, serum insulin, triglycerides and LDL-Cholesterol levels of db/db mice. These findings suggest the therapeutic efficacy of the DeoAn for type 2 diabetes mellitus and can be potential phytochemical for its management.
骨骼肌是餐后葡萄糖利用的主要部位,增加该组织的葡萄糖利用速率可能有助于控制与糖尿病相关的高血糖。在这里,我们研究了从穿心莲中分离得到的去氧穿心莲内酯(DeoAn)对骨骼肌葡萄糖利用的影响,并在链脲佐菌素诱导的糖尿病大鼠和遗传性糖尿病 db/db 小鼠体内研究了其抗高血糖作用。在 L6 肌管中,DeoAn 通过增强葡萄糖转运蛋白 4(GLUT4)向细胞表面的易位,剂量依赖性地刺激葡萄糖摄取,而不影响总细胞 GLUT4 和 GLUT1 含量。DeoAn 的这些作用与胰岛素具有相加作用。进一步的分析表明,DeoAn 激活了 PI-3-K 和 AMPK 依赖性信号通路,这解释了 L6 肌管中葡萄糖转运的增加。此外,DeoAn 降低了链脲佐菌素诱导的糖尿病大鼠的餐后血糖水平,也抑制了 db/db 小鼠的空腹血糖、血清胰岛素、甘油三酯和 LDL-Cholesterol 水平的升高。这些发现表明,DeoAn 对 2 型糖尿病具有治疗功效,并且可以作为其管理的潜在植物化学物质。