Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.
Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.
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DOI：
10.1371/journal.pone.0032718
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tan BK
中科院分区：
文献类型：
--
作者：
Ong KW;Hsu A;Tan BK
绿原酸（CGA）已被证明可以延迟肠道葡萄糖吸收并抑制糖异生。我们的目的是研究 CGA 在从 db/db 小鼠和 L6 骨骼肌细胞分离的骨骼肌中葡萄糖转运调节中的作用。对用CGA处理的db/db小鼠进行口服葡萄糖耐量测试，并分离比目鱼肌用于2-脱氧葡萄糖转运研究。还在使用或不使用渥曼青霉素或化合物 c 等抑制剂的情况下检查了 L6 肌管中的 2DG 转运。用 AMPKα1/2 siRNA 敲低 AMPK，以研究其对 CGA 刺激的葡萄糖转运的影响。在 CGA 存在的情况下，研究了 GLUT 4 易位、AMPK 和 Akt 磷酸化、AMPK 活性以及 IRS-1 和 PI3K 的关联。在 db/db 小鼠中，腹腔注射 250 mg/kg CGA 后 10 分钟观察到空腹血糖显着降低，并且在葡萄糖激发后该效果持续持续 30 分钟。此外，CGA 刺激并增强了比目鱼肌中基础和胰岛素介导的 2DG 转运。在 L6 肌管中，CGA 导致葡萄糖转运呈剂量和时间依赖性增加。化合物 c 和 AMPKα1/2 siRNA 消除了 CGA 刺激的葡萄糖转运。与这些结果一致，发现 CGA 磷酸化 AMPK 和 ACC，与 AMPK 活性增加的结果一致。 CGA 似乎没有增强 IRS-1 与 p85 的关联。然而，我们观察到 CGA 激活 Akt。这些并行激活反过来又增加了 GLUT 4 向质膜的易位。在 2 mmol/l 时，CGA 不会对 L6 肌管的活力或增殖造成任何显着变化。我们的数据首次证明 CGA 通过激活 AMPK 来刺激骨骼肌中的葡萄糖转运。看来 CGA 可能有助于咖啡对 2 型糖尿病的有益作用。
Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus.
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影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
DOI：
10.1111/j.1365-2362.2010.02455.x
发表时间：
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