14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive component of Andrographis paniculata, has antidiabetic activity. AMP-activated protein kinase (AMPK) regulates glucose transport and ameliorates insulin resistance. The aim of the present study was to investigate whether activation of AMPK is involved in the mechanism by which deAND ameliorates insulin resistance in muscles. deAND amounts up to 40 μM dose-dependently activated phosphorylation of AMPKα and TBC1D1 in C2C12 myotubes. In addition, deAND significantly activated phosphorylation of LKB1 at 6 h after treatment, and this activation was maintained up to 48 h. deAND increased glucose uptake at 18 h after treatment, and this increase was time dependent up to 72 h. Compound C, an inhibitor of AMPK, suppressed deAND-induced phosphorylation of AMPKα and TBC1D1 and reversed the effect on glucose uptake. In addition, the expression of GLUT4 mRNA and protein in C2C12 myotubes was up-regulated by deAND in a time-dependent manner. Promotion of GLUT4 gene transcription was verified by a pGL3-GLUT4 (837 bp) reporter assay. deAND also increased the nuclear translocation of MEF-2A and PPARβ. After 16 weeks of feeding, the high-fat diet (HFD) inhibited phosphorylation of AMPKα and TBC1D1 in skeletal muscle of obese C57BL/6JNarl mice, and deactivation of AMPKα and TBC1D1 by the HFD was abolished by deAND supplementation. Supplementation with deAND significantly promoted membrane translocation of GLUT4 compared with the HFD group. Supplementation also significantly increased GLUT4 mRNA and protein expression in skeletal muscle compared with the HFD group. The hypoglycemic effects of deAND are likely associated with activation of the LKB1/AMPKα/TBC1D1/GLUT4 signaling pathway and stimulation of MEF-2A- and PPARβ-dependent GLUT4 gene expression, which account for the glucose uptake into skeletal muscle and lower blood glucose levels.

中文翻译：

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14-Deoxy-11,12-Didehydroandrographolide 改善葡萄糖耐受不良，增强 LKB1/AMPKα/TBC1D1/GLUT4 信号通路并诱导肥胖小鼠肌管和骨骼肌中 GLUT4 的表达

14-Deoxy-11,12-didehydroandrographolide (deAND)，一种生物活性成分穿心莲，具有抗糖尿病活性。AMP 活化蛋白激酶 (AMPK) 调节葡萄糖转运并改善胰岛素抵抗。本研究的目的是调查 AMPK 的激活是否与 deAND 改善肌肉胰岛素抵抗的机制有关。deAND 金额高达 40μM 剂量依赖性激活的 AMPK 磷酸化α和 C2C12 肌管中的 TBC1D1。此外，deAND 在处理后 6 小时显着激活了 LKB1 的磷酸化，并且这种激活一直持续到 48 小时。deAND 在治疗后 18 小时增加葡萄糖摄取，并且这种增加在 72 小时内呈时间依赖性。AMPK抑制剂化合物C抑制deAND诱导的AMPK磷酸化α和 TBC1D1 并逆转对葡萄糖摄取的影响。此外，deAND 以时间依赖性方式上调 C2C12 肌管中 GLUT4 mRNA 和蛋白质的表达。推广过剩4通过 pGL3-GLUT4 (837 bp) 报告基因分析验证基因转录。deAND 还增加了 MEF-2A 和 PPAR 的核转位β. 喂食 16 周后，高脂饮食 (HFD) 抑制了 AMPK 的磷酸化α肥胖 C57BL/6JNarl 小鼠骨骼肌中的 TBC1D1 和 AMPK 失活α和 HFD 的 TBC1D1 被 deAND 补充废除。与 HFD 组相比，补充 deAND 显着促进了 GLUT4 的膜易位。与 HFD 组相比，补充剂还显着增加了骨骼肌中 GLUT4 mRNA 和蛋白质的表达。deAND 的降血糖作用可能与 LKB1/AMPK 的激活有关α/TBC1D1/GLUT4信号通路和MEF-2A-和PPAR的刺激β依赖的过剩4基因表达，这解释了骨骼肌吸收葡萄糖和降低血糖水平。