title: Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.
abstract: Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Miao
authors: M
authors: Xu
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Yuanyuan
authors: Y
authors: Xiao
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Jun
authors: J
authors: Yin
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Wolin
authors: W
authors: Hou
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Xueying
authors: X
authors: Yu
authors: Department of Clinical Nutrition, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Li
authors: L
authors: Shen
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Fang
authors: F
authors: Liu
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Li
authors: L
authors: Wei
authors: Shanghai Clinical Center for Diabetes, Shanghai Clinical Center for Metabolic Diseases, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Weiping
authors: W
authors: Jia
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000106:Acetate-CoA Ligase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D034741:RNA, Small Interfering; D001599:Berberine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C526181:PRKAA2 protein, human; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000106:Acetate-CoA Ligase; D042967:Electron Transport Complex I; D005947:Glucose