Glucose consumption assay discovered a novel compound from natural product with beneficial effects on diabetic mice via AMPK activation

[Speaker] Xiuying Yang:1
[Co-author] Li-Li Shi:1, Wei-Hua Jia:1, Li Zhang:1, Chun-Yang Xu:1, Xi Chen:1, Lin Yin:1, Lian-Hua Fang:1, Gui-Fen Qiang:1, Guan-Hua Du:1
1:State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica of Peking Union Medical College, Beijing, China

AIM: We established a cell-based assay to screen compounds that can regulate glucose metabolism with anti-diabetic effects. Using this platform, we acquired a natural product for further evaluation.
Methods: Human hepatoma cells (HepG2) and skeletal muscle myotube (L6) were used to investigate the effect of compounds on glucose consumption and the related mechanisms. Normal ICR mice, alloxan-induced type 1 diabetic mice and type 2 diabetes mice (KKay mice) were employed to explore the effect of compound on glucose metabolism in vivo.
Results: We found that a natural compound-Coptsine increased the glucose consumption and glucose uptake in HepG2 cells and L6 myotube. Coptsine is one of the major compounds in plant Coptis. Coptisine increased ATP level in HepG2 cells and decreased mitochondrial membrane potential in HepG2 cells. Coptisine promoted the hepatic mitochondrial F0F1-ATPase activity. Coptisine can increase AMPK phosphorylation level, which is close related to the effect of glucose metabolism. Coptisine (10 mg/kg) decreased both normal and diabetic (type 1, type 2) mice blood glucose level in vivo.
Conclusion: In summary, basing on our economic cell-based assay for glucose consumption, we found the natural product coptisine maybe a novel hypoglycemic drug.
Fundations: CAMS Initiative for Innovative Medicine (CAMS-I2M) 2016-I2M-3-007. National Natural Science Foundation of China, 81470159

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