2024
1571-P: CIDEB and CGI-58 Regulate Liver Lipid Droplet Size with Cholesterol Content, Linking to Inflammation and Fibrosis in Metabolic Dysfunction–Associated Steatohepatitis
SAKUMA I, GASPAR R, NASIRI A, KAHN M, ZHENG J, GUERRA M, YIMLAMAI D, MURRAY S, PERELIS M, BARNES W, VATNER D, PETERSEN K, SAMUEL V, SHULMAN G. 1571-P: CIDEB and CGI-58 Regulate Liver Lipid Droplet Size with Cholesterol Content, Linking to Inflammation and Fibrosis in Metabolic Dysfunction–Associated Steatohepatitis. Diabetes 2024, 73 DOI: 10.2337/db24-1571-p.Peer-Reviewed Original ResearchLipid droplet sizeCGI-58Choline-deficient l-amino acid-defined high-fat dietGlycerol-3-phosphate acyltransferaseAntisense oligonucleotidesComparative gene identification-58Glycerol-3-phosphateLoss of function mutationsLipid droplet morphologyExpression of CGI-58Liver inflammationCidebCholesterol contentFunction mutationsL-amino acid-defined high-fat dietComplications of type 2 diabetesMolecular mechanismsDevelopment of liver inflammationMacrophage crown-like structuresType 2 diabetesHigh-fat dietCrown-like structuresASO treatmentGPAMKnockdown
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 balanceA Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance
Lyu K, Zhang Y, Zhang D, Kahn M, Ter Horst KW, Rodrigues MRS, Gaspar RC, Hirabara SM, Luukkonen PK, Lee S, Bhanot S, Rinehart J, Blume N, Rasch MG, Serlie MJ, Bogan JS, Cline GW, Samuel VT, Shulman GI. A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance. Cell Metabolism 2020, 32: 654-664.e5. PMID: 32882164, PMCID: PMC7544641, DOI: 10.1016/j.cmet.2020.08.001.Peer-Reviewed Original ResearchConceptsPlasma membraneEndoplasmic reticulumHigh-fat diet-induced hepatic insulin resistanceSubcellular fractionation methodInsulin receptor kinaseKey lipid speciesHepatic insulin resistanceDiet-induced hepatic insulin resistanceReceptor kinaseDiacylglycerol acyltransferase 2Molecular mechanismsAcute knockdownPhosphorylationLipid dropletsLipid speciesAcyltransferase 2KnockdownLiver-specific overexpressionDAG accumulationPKCϵDAG contentMembraneFractionation methodKinaseMitochondria
1999
Regulation of myocardial glucose uptake and transport during ischemia and energetic stress
Young L, Russell R, Yin R, Caplan M, Ren J, Bergeron R, Shulman G, Sinusas A. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. The American Journal Of Cardiology 1999, 83: 25-30. PMID: 10750583, DOI: 10.1016/s0002-9149(99)00253-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnergetic stressEnergy-generating metabolic pathwaysMonophosphate-activated protein kinaseGlucose uptakeGlucose transport proteinProtein kinaseTransporter translocationTransport proteinsMolecular mechanismsMetabolic pathwaysCardiac glucose uptakeGlucose transporterCellular mechanismsGlucose transportFuel gaugeKinaseTranslocationGlucose entryModerate regional ischemiaSubsequent metabolismGlucose utilization increasesImportant roleUptakeGLUT4Stress