2022
Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis
LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI. Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122287119. PMID: 35238637, PMCID: PMC8916010, DOI: 10.1073/pnas.2122287119.Peer-Reviewed Original ResearchConceptsGlucose-lowering effectPlasma glucose concentrationComplex I activityHepatic gluconeogenesisType 2 diabetes mellitusGlucose concentrationGlycerol-3-phosphate dehydrogenase activityI activityDiabetes mellitusSelective inhibitionMetforminInhibitionRelevant concentrationsGluconeogenesisPhenforminVivoMost studiesDehydrogenase activityGalegineMellitus
2020
Cellular and Molecular Mechanisms of Metformin Action
LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews 2020, 42: 77-96. PMID: 32897388, PMCID: PMC7846086, DOI: 10.1210/endrev/bnaa023.Peer-Reviewed Original ResearchConceptsGlucose-lowering effectType 2 diabetesMetformin actionHepatic gluconeogenesisFirst-line therapyDosage of metforminRedox-dependent mechanismMechanism of actionMolecular mechanismsSafety profileMetformin inhibitsComplex I inhibitionMetformin concentrationsGlucose metabolismMetforminClinical settingPleotropic effectsDiscrepant effectsDiabetesAMPK activationCurrent literatureRelevant concentrationsI inhibitionRecent studiesRedox balance