文献类型：期刊文献

英文题名：Multiple Comparisons of Glucokinase Activation Mechanisms of Five Mulberry Bioactive Ingredients in Hepatocyte

作者：He, Hao[1,2]; Yu, Wan-Guo[1,2]; Yang, Jun-Peng[1,2]; Ge, Sheng[3]; Lu, Yan-Hua[1,2]

机构：[1] State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Box 283, 130 Meilong Road, Shanghai, 200237, China; [2] Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai, 200237, China; [3] Clinical Nutrition Department, Shanghai Jiaotong University, Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China

年份：2016

卷号：64

期号：12

起止页码：2475

外文期刊名：Journal of Agricultural and Food Chemistry

收录：EI(收录号：20161602273407)

语种：英文

外文关键词：Physiology - Glucose - Binding energy - Plants (botany) - Proteins - Hydrogen bonds

摘要：Glucokinase (GK) activity, which is rapidly regulated by glucokinase regulatory protein (GKRP) in the liver, is crucial for blood glucose homeostasis. In this paper, the GK activation mechanisms of 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were compared. The results revealed that DNJ, RES, C3G, and C3R could differently improve glucose consumption and enhance intracellular GK activities. DNJ and RES significantly promoted GK translocation at 12.5 μM, whereas other ingredients showed moderate effects. DNJ, C3G, and C3R could rupture intramolecular hydrogen bonds of GK to accelerate its allosteric activation at early stage. RES and OXY could bind to a "hydrophobic pocket" on GK to stabilize the active GK at the final stage. Otherwise, RES, OXY, C3G, and C3R could interact with GKRP at the F1P binding site to promote GK dissociation and translocation. Enzymatic assay showed that RES (15-50 μM) and OXY (25-50 μM) could significantly enhance GK activities, which was caused by their binding properties with GK. Moreover, the most dramatic up-regulation effects on GK expression were observed in C3G and C3R groups. This work expounded the differences between GK activation mechanisms, and the new findings would help to develop new GK activators. ? 2015 American Chemical Society.