title: Multiple Comparisons of Glucokinase Activation Mechanisms of Five Mulberry Bioactive Ingredients in Hepatocyte.
abstract: 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.
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.|Shanghai Collaborative Innovation Center for Biomanufacturing Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.
authors: Hao
authors: H
authors: He
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.|Shanghai Collaborative Innovation Center for Biomanufacturing Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.
authors: Wan-Guo
authors: WG
authors: Yu
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.|Shanghai Collaborative Innovation Center for Biomanufacturing Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.
authors: Jun-Peng
authors: JP
authors: Yang
authors: Clinical Nutrition Department, Shanghai Jiaotong University Affiliated Sixth People's Hospital , Shanghai 200233, People's Republic of China.
authors: Sheng
authors: S
authors: Ge
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.|Shanghai Collaborative Innovation Center for Biomanufacturing Technology , 130 Meilong Road, Shanghai 200237, People's Republic of China.
authors: Yan-Hua
authors: YH
authors: Lu
mesh_terms: D017485:1-Deoxynojirimycin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000872:Anthocyanins / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000872:Anthocyanins; D001786:Blood Glucose; D002352:Carrier Proteins; C485100:GCKR protein, human; D005960:Glucosides; D010936:Plant Extracts; D013267:Stilbenes; C462279:cyanidin-3-O-beta-glucopyranoside; C080906:glucokinase regulatory protein; D017485:1-Deoxynojirimycin; C034912:puag-haad; D005941:Glucokinase; D005947:Glucose; C428983:cyanidin 3-rutinoside; D000077185:Resveratrol
keywords: glucokinase; glucokinase regulatory protein; glucose homeostasis; mulberry