title: Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex.
abstract: Metformin is the most widely prescribed oral anti-diabetic agent. Recently, we have shown that low metformin concentrations found in the portal vein suppress glucose production in hepatocytes through activation of AMPK. Moreover, low concentrations of metformin were found to activate AMPK by increasing the phosphorylation of AMPKα at Thr-172. However, the mechanism underlying the increase in AMPKα phosphorylation at Thr-172 and activation by metformin remains unknown. In the current study, we find that low concentrations of metformin promote the formation of the AMPK αβγ complex, resulting in an increase in net phosphorylation of the AMPK α catalytic subunit at Thr-172 by augmenting phosphorylation by LKB1 and antagonizing dephosphorylation by PP2C.
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Shumei
authors.initials: S
authors.lastname: Meng
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: He
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Lishou
authors.initials: L
authors.lastname: Xiong
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Evan
authors.initials: E
authors.lastname: Chang
authors.affiliation: Endocrinology, Departments of Pediatrics, Physiology, and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
authors.forename: Sally
authors.initials: S
authors.lastname: Radovick
authors.affiliation: From the Divisions of Metabolism and.
authors.forename: Fredric E
authors.initials: FE
authors.lastname: Wondisford
authors.affiliation: From the Divisions of Metabolism and heling@jhmi.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: He
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D021122:Protein Subunits; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D054648:Protein Phosphatase 2
keywords: AMP-activated Kinase (AMPK); Gene Regulation; Glucose Metabolism; Liver Kinase B1 (LKB1); Metformin; Protein Phosphatase 2C (PP2C)