2001
Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
Zhang C, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig A, Boss O, Kim Y, Zheng X, Wheeler M, Shulman G, Chan C, Lowell B. Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes. Cell 2001, 105: 745-755. PMID: 11440717, DOI: 10.1016/s0092-8674(01)00378-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBlood GlucoseBody WeightDiabetes MellitusDiabetes Mellitus, Type 2Disease Models, AnimalGene TargetingHomeostasisHumansHyperglycemiaInsulinInsulin SecretionIon ChannelsIslets of LangerhansMaleMembrane Transport ProteinsMiceMice, KnockoutMice, ObeseMitochondrial ProteinsModels, BiologicalObesityProteinsRNA, MessengerThermogenesisUncoupling AgentsUncoupling Protein 2ConceptsOb/ob miceInsulin secretionOb miceCell dysfunctionFirst-phase insulin secretionIslet ATP levelsGlucose-stimulated insulin secretionLevel of glycemiaSerum insulin levelsBeta-cell dysfunctionType 2 diabetesObesity-induced diabetesΒ-cell dysfunctionBeta-cell glucose sensingProtein 2UCP2-deficient miceInsulin levelsPathophysiologic significanceBeta cellsType 2SecretionMiceObesityATP levelsDiabetesAdipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
Abel E, Peroni O, Kim J, Kim Y, Boss O, Hadro E, Minnemann T, Shulman G, Kahn B. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001, 409: 729-733. PMID: 11217863, DOI: 10.1038/35055575.Peer-Reviewed Original ResearchConceptsInsulin-stimulated glucose uptakeType 2 diabetesInsulin resistanceGlucose uptakeAdipose tissueGLUT4 expressionInsulin-resistant statesDownregulation of GLUT4Glucose intoleranceGlucose transportAdipose massIntracellular storage sitesGlucose homeostasisInsulin actionDiabetesPhosphoinositide-3-OH kinaseImpaired activationSkeletal muscleMuscleMicePlasma membrane4Early defectsLiverMain siteAdipocytes
1985
Metabolic Response to Three Years of Continuous, Basal Rate Intravenous Insulin Infusion in Type II Diabetic Patients*
BLACKSHEAR P, SHULMAN G, ROUSSELL A, NATHAN D, MINAKER K, ROWE J, ROBBINS D, COHEN A. Metabolic Response to Three Years of Continuous, Basal Rate Intravenous Insulin Infusion in Type II Diabetic Patients*. The Journal Of Clinical Endocrinology & Metabolism 1985, 61: 753-760. PMID: 3897260, DOI: 10.1210/jcem-61-4-753.Peer-Reviewed Original ResearchConceptsType II diabetic patientsII diabetic patientsInsulin clamp studiesDiabetic patientsInsulin infusionClamp studiesObese type II diabetic patientsEuglycemic insulin clamp studiesInfusion pumpVitreous fluorescein concentrationHemoglobin A1c levelsMonths of treatmentGlucose disposal rateIntravenous insulin infusionNormal glycemic controlSerum triglyceride concentrationBlood glucose levelsInfusion of insulinImplantable infusion pumpInsulin infusion pumpA1c levelsGlycemic controlSignificant hypoglycemiaImmunoreactive insulinPlasma glucose