2023
MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis.
Park J, Hall C, Hubbard B, LaMoia T, Gaspar R, Nasiri A, Li F, Zhang H, Kim J, Haeusler R, Accili D, Shulman G, Yu H, Choi E. MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis. Diabetes 2023, 72: 1781-1794. PMID: 37725942, PMCID: PMC10658066, DOI: 10.2337/db23-0314.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndocytosisGlucoseHomeostasisInsulinInsulin ResistanceLiverMad2 ProteinsMaleMiceReceptor, InsulinConceptsIR endocytosisInsulin receptor endocytosisCell division regulatorsInsulin receptorProlongs insulin actionReceptor endocytosisTranscriptomic profilesInsulin stimulationEndocytosisMetabolic homeostasisCell surfaceGenetic ablationMetabolic functionsInsulin actionP31cometMad2BubR1DisruptionSignalingRegulatorHomeostasisAdipose tissueInteractionHepatic fat accumulationMetabolism
2020
A 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