2021
282-OR: The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation and Pyruvate Carboxylase Flux in Man Assessed by Positional Isotopomer NMR Tracer Analysis (PINTA)
PETERSEN K, SHULMAN G. 282-OR: The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation and Pyruvate Carboxylase Flux in Man Assessed by Positional Isotopomer NMR Tracer Analysis (PINTA). Diabetes 2021, 70 DOI: 10.2337/db21-282-or.Peer-Reviewed Original ResearchHepatic mitochondrial oxidationPhysiological increaseSpouse/partnerDual agonistsGilead SciencesJanssen ResearchTreatment of T2DPlasma glucagon concentrationsNovo NordiskMitochondrial oxidationEffect of glucagonPyruvate carboxylase fluxMitochondrial fat oxidationAnorexic effectGlucagon concentrationsHepatic steatosisClinical trialsC-peptideGLP-1Food intakeHealthy volunteersFat oxidationIonis PharmaceuticalsGlucagonGlucose production
2020
220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 Inhibition
GALSGAARD K, WEWER ALBRECHTSEN N, HOLST J, SHULMAN G, PETERSEN K, NASIRI A, CLINE G, ZHANG X, LEE J, HUBBARD B. 220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 Inhibition. Diabetes 2020, 69 DOI: 10.2337/db20-220-lb.Peer-Reviewed Original ResearchSpouse/partnerDohme Corp.Hepatic autophagyMerck SharpKidney diseaseNovo Nordisk A/SAMP kinaseGlucagon treatmentPlasma glucagon concentrationsAdvisory PanelKrebs-Henseleit bicarbonate bufferHepatic protein metabolismNational InstituteNovo Nordisk FoundationMarkers of autophagyHepatic glucose metabolismFasted male ratsProtein/amino acid metabolismGlucagon's roleGlucagon concentrationsGlucagon infusionMale ratsAwake miceNovo Nordisk A/S.Glucose metabolismGlucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout mice
2018
Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis
PERRY R, WANG Y, BRILL A, PENG L, ZHANG D, DUFOUR S, ZHANG Y, ZHANG X, NOZAKI Y, CLINE G, EHRLICH B, PETERSEN K, SHULMAN G. Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis. Diabetes 2018, 67 DOI: 10.2337/db18-146-or.Peer-Reviewed Original ResearchSpouse/partnerHigh-fat diet-induced hepatic steatosisNonalcoholic fatty liver diseaseDiet-induced hepatic steatosisGilead SciencesFatty liver diseasePlasma glucagon concentrationsType 2 diabetesHepatic acetyl-CoA contentLiver-specific knockdownIntracellular calcium signalingMitochondrial oxidationGlucose intoleranceAdipocyte triglyceride lipaseLiver diseaseWT miceGlucagon concentrationsHepatic steatosisGlucagon infusionAcetyl-CoA contentChronic increaseHepatic mitochondrial oxidationGlucagon biologyGlucagon stimulationKnockout miceMechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats
PERRY R, SONG J, WANG Y, SHULMAN G. Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats. Diabetes 2018, 67 DOI: 10.2337/db18-254-or.Peer-Reviewed Original ResearchSodium-glucose transport protein 2 inhibitorsHepatic glucose productionEffect of dapagliflozinEuglycemic ketoacidosisHepatic ketogenesisVolume depletionGlucose productionPlasma catecholaminesWhite adipose tissue lipolysisPlasma glucagon concentrationsExtracellular volume depletionPlasma insulin levelsAdipose tissue lipolysisPlasma insulin concentrationHepatic acetyl-CoA contentNormal Sprague-DawleyICV injectionWAT lipolysisInsulin levelsFurosemide treatmentGlucagon concentrationsAcetyl-CoA contentSaline infusionTissue lipolysisInsulin concentrations
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 ResearchConceptsInsulin-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
1995
Contribution of Hepatic Glycogenolysis to Glucose Production in Humans in Response to a Physiological Increase in Plasma Glucagon Concentration
Magnusson I, Rothman D, Gerard D, Katz L, Shulman G. Contribution of Hepatic Glycogenolysis to Glucose Production in Humans in Response to a Physiological Increase in Plasma Glucagon Concentration. Diabetes 1995, 44: 185-189. PMID: 7859939, DOI: 10.2337/diab.44.2.185.Peer-Reviewed Original ResearchConceptsNet hepatic glycogenolysisLiver glycogen concentrationPlasma glucagon concentrationsHepatic glycogenolysisGlucagon concentrationsGlycogen concentrationLiver volumeGlucose productionPlasma glucose concentrationOverall glucose productionTwo-compartment modelHealthy subjectsPhysiological incrementsPhysiological increaseGlucose appearanceSame time periodMagnetic resonance imagesGlucose kineticsBaseline RaInfusionGlycogenolysisGlucose concentrationResonance imagesMumolContribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration
Magnusson I, Rothman D, Gerard D, Katz L, Shulman G. Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration. Diabetes 1995, 44: 185-189. DOI: 10.2337/diabetes.44.2.185.Peer-Reviewed Original Research
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
1978
Glucose Disposal during Insulinopenia in Somatostatin-Treated Dogs
Shulman G, Liljenquist J, Williams P, Lacy W, Cherrington A. Glucose Disposal during Insulinopenia in Somatostatin-Treated Dogs. Journal Of Clinical Investigation 1978, 62: 487-491. PMID: 670404, PMCID: PMC371787, DOI: 10.1172/jci109150.Peer-Reviewed Original ResearchConceptsNet hepatic glucose uptakeHepatic glucose productionHepatic glucose uptakeGlucagon secretionHepatic glucose storageBasal insulinGlucagon levelsGlucose storageNet hepatic glucose productionGlucose productionGlucose uptakeAbility of hyperglycemiaPancreatic hormone releasePlasma glucagon concentrationsPlasma glucagon levelsInduction of hyperglycemiaPlasma glucose levelsPlasma glucose concentrationHepatic glucose balanceIntraportal insulinGlucagon concentrationsConscious dogsSomatostatin inhibitionGlucagon infusionGlucose disposal