2001
NMR Spectroscopy in β Cell Engineering and Islet Transplantation
PAPAS K, COLTON C, GOUNARIDES J, ROOS E, JAREMA M, SHAPIRO M, CHENG L, CLINE G, SHULMAN G, WU H, BONNER‐WEIR S, WEIR G. NMR Spectroscopy in β Cell Engineering and Islet Transplantation. Annals Of The New York Academy Of Sciences 2001, 944: 96-119. PMID: 11797699, DOI: 10.1111/j.1749-6632.2001.tb03826.x.Peer-Reviewed Original ResearchConceptsIslet transplantationGlucose metabolismBeta cellsLong-term complicationsIrreversible damageTerm complicationsOxidative glucose metabolismAcute ischemiaTransplantationVivo efficacyHuman isletsIslet preparationsC-myc oncogeneSecreting tissueCell damageSuch exposureGenetic alterationsBcl-2Overnight incubationIslet transportationIsletsUncoupling 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 levelsDiabetesInsulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)
Cho H, Mu J, Kim J, Thorvaldsen J, Chu Q, Crenshaw E, Kaestner K, Bartolomei M, Shulman G, Birnbaum M. Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ). Science 2001, 292: 1728-1731. PMID: 11387480, DOI: 10.1126/science.292.5522.1728.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDeoxyglucoseDiabetes Mellitus, Type 2FemaleGene TargetingGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHomeostasisInsulinInsulin ResistanceIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionConceptsSerine-threonine protein kinase AktProtein kinase Akt2Protein kinase AktProtein kinase B.Activation of phosphatidylinositolEssential genesKinase Akt2Kinase AktAbility of insulinGlucose homeostasisNormal glucose homeostasisAkt2Critical initial stepEarly eventsSkeletal muscleHomeostasisInsulin actionMice LackingInsulin responsivenessInitial stepActivationInsulin resistancePhosphatidylinositolBlood glucoseGenes
1998
Disruption of IRS-2 causes type 2 diabetes in mice
Withers D, Gutierrez J, Towery H, Burks D, Ren J, Previs S, Zhang Y, Bernal D, Pons S, Shulman G, Bonner-Weir S, White M. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998, 391: 900-904. PMID: 9495343, DOI: 10.1038/36116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCloning, MolecularDiabetes Mellitus, Type 2FemaleGene TargetingHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationReceptor, InsulinRecombination, GeneticSignal TransductionConceptsType 2 diabetesInsulin resistanceHuman type 2 diabetesPancreatic β-cell functionInsulin secretion increasesSingle molecular abnormalityΒ-cell compensationIRS-2-deficient miceΒ-cell functionHuman type 2Insulin secretionInsulin receptor substrateGlucose homeostasisSecretion increasesInsulin actionType 2DiabetesMolecular abnormalitiesProgressive deteriorationSkeletal muscleIRS-2Insulin signalingIRS-1Mild resistanceMice
1996
Time course of the defective α-cell response to hypoglycemia in diabetic BB rats
Jacob R, Dziura J, Morgen J, Shulman G, Sherwin R. Time course of the defective α-cell response to hypoglycemia in diabetic BB rats. Metabolism 1996, 45: 1422-1426. PMID: 8931649, DOI: 10.1016/s0026-0495(96)90125-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1GlucagonHypoglycemiaInsulinIslets of LangerhansMaleNorepinephrineRatsRats, Inbred BBTime FactorsConceptsInsulin-dependent diabetes mellitusDays of diabetesBB ratsBB/Wor ratsNondiabetic BB ratsΑ-cell responseDiabetic BB ratsCourse of diabetesPancreatic glucagon levelsPancreatic glucagon contentBeta-cell functionPancreatic insulin contentHypoglycemic challengeCounterregulatory responsesDiabetes onsetDiabetes mellitusGlucagon levelsGlucagon releasePlasma glucagonGlucagon concentrationsInsulin clampGlucagon contentBaseline plasmaDisease onsetGroup 2
1993
Comparative Effects of Monomethylsuccinate and Glucose on Insulin Secretion from Perifused Rat Islets
Zawalich W, Zawalich K, Cline G, Shulman G, Rasmussen H. Comparative Effects of Monomethylsuccinate and Glucose on Insulin Secretion from Perifused Rat Islets. Diabetes 1993, 42: 843-850. PMID: 8388341, DOI: 10.2337/diab.42.6.843.Peer-Reviewed Original ResearchConceptsPhosphoinositide hydrolysisInsulin secretionCalcium channel antagonist nitrendipineChannel antagonist nitrendipinePerifused rat isletsCalcium channel antagonistsSecond phase releaseGut hormone cholecystokininFirst-phase releaseInsulinotropic effectAntagonist nitrendipineSulfonylurea tolbutamideChannel antagonistsInsulin releaseHormone cholecystokininSubsequent stimulationGlucose-induced responseRat isletsSustained increaseStimulatory effectBiphasic patternMM glucoseMMSuccSecretionMonomethylsuccinate
1987
Physiological Role of Cholecystokinin in Meal-Induced Insulin Secretion in Conscious Rats: Studies With L 364718, A Specific Inhibitor of CCK-Receptor Binding
Rossetti L, Shulman G, Zawalich W. Physiological Role of Cholecystokinin in Meal-Induced Insulin Secretion in Conscious Rats: Studies With L 364718, A Specific Inhibitor of CCK-Receptor Binding. Diabetes 1987, 36: 1212-1215. PMID: 3308589, DOI: 10.2337/diab.36.10.1212.Peer-Reviewed Original ResearchConceptsPlasma insulinPostprandial plasma insulinGut hormone cholecystokininImportant physiologic roleCCK receptor bindingIntraduodenal catheterInsulin outputPrior administrationConscious ratsEnteroinsular axisGlucagon concentrationsVehicle injectionCCK antagonistsCCK secretionProtein ingestionInsulin secretionSpecific antagonistHormone cholecystokininCholecystokininPhysiologic roleInsulinAntagonistGlucagonRatsVivo regulation