Department of Oncology, The 174th Hospital of the Chinese People's Liberation Army, The Affiliated Chenggong Hospital of Xiamen University, Xiamen 361003, Fujian, People's Republic of China.
Mol Cell Biochem. 2012 Sep;368(1-2):69-76. doi: 10.1007/s11010-012-1344-5. Epub 2012 May 30.
Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.
二甲双胍通过激活 5'-腺苷一磷酸激活蛋白激酶（AMPK）发挥能量调节作用，AMPK 是调节能量平衡的关键因子，但 AMPK 是否为其直接靶标尚不确定。本研究旨在探讨二甲双胍与 AMPK 之间可能的相互作用。首先，我们通过 Western blot 验证了二甲双胍可促进人 HepG2 细胞中 AMPK 的激活并诱导 ACC 失活。然后，我们通过分子对接分析预测二甲双胍可能与 AMPK 的γ亚基相互作用。荧光光谱和 ForteBio 测定表明，与 AMPK 的α亚基相比，二甲双胍与 γ 亚基具有更强的结合能力。此外，二甲双胍与 γ-AMPK 的相互作用导致 CD 光谱测定的α螺旋性降低，但与 α-AMPK 相比，变化相对较小。这些结果表明，二甲双胍可能通过与 γ 亚基结合与 AMPK 相互作用。
