2020
Glucagon 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
2014
Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis
Perry RJ, Zhang XM, Zhang D, Kumashiro N, Camporez JP, Cline GW, Rothman DL, Shulman GI. Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nature Medicine 2014, 20: 759-763. PMID: 24929951, PMCID: PMC4344321, DOI: 10.1038/nm.3579.Peer-Reviewed Original Research
2001
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim J, Fillmore J, Chen Y, Yu C, Moore I, Pypaert M, Lutz E, Kako Y, Velez-Carrasco W, Goldberg I, Breslow J, Shulman G. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 7522-7527. PMID: 11390966, PMCID: PMC34701, DOI: 10.1073/pnas.121164498.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseFatty Acids, NonesterifiedGlucagonGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHeterozygoteInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinLipoprotein LipaseLiverMiceMice, KnockoutMice, TransgenicMuscle, SkeletalOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphoproteinsSignal TransductionTriglyceridesConceptsInsulin resistanceFatty acid-derived metabolitesInsulin actionTriglyceride contentType 2 diabetes mellitusInsulin activationLipoprotein lipaseInsulin receptor substrate-1-associated phosphatidylinositolMuscle triglyceride contentSkeletal muscleTissue-specific insulin resistanceLiver triglyceride contentAdipocyte-derived hormoneHyperinsulinemic-euglycemic clampEndogenous glucose productionLiver-specific overexpressionTissue-specific overexpressionInsulin-stimulated glucose uptakeDiabetes mellitusTissue-specific increaseTransgenic miceGlucose productionFat metabolismGlucose uptakeInsulin
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
Local Ventromedial Hypothalamus Glucopenia Triggers Counterregulatory Hormone Release
Borg W, Sherwin R, During M, Borg M, Shulman G. Local Ventromedial Hypothalamus Glucopenia Triggers Counterregulatory Hormone Release. Diabetes 1995, 44: 180-184. PMID: 7859938, DOI: 10.2337/diab.44.2.180.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusFrontal lobeMicrodialysis probeCounterregulatory hormone releaseCellular glucopeniaCounterregulatory hormonesCounterregulatory responsesPlasma glucagonPlasma glucoseLocal perfusionHormone releaseCerebral tissueStriking elevationControl groupGlucopeniaBrain tissueGlucopenic agentHypoglycemiaRatsTwofold increaseLobeTissueNorepinephrineHypothalamusEpinephrineContribution 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 imagesMumol
1993
Inhibitory Effect of Pregnancy on Counterregulatory Hormone Responses to Hypoglycemia in Awake Rat
Rossi G, Lapaczewski P, Diamond M, Jacob R, Shulman G, Sherwin R. Inhibitory Effect of Pregnancy on Counterregulatory Hormone Responses to Hypoglycemia in Awake Rat. Diabetes 1993, 42: 1440-1445. PMID: 8375583, DOI: 10.2337/diab.42.10.1440.Peer-Reviewed Original ResearchConceptsPregnant ratsGlucagon responseNonpregnant controlsAwake pregnant ratsCounterregulatory hormone responsesIntensive insulin treatmentRelease of epinephrineHypoglycemia risk factorsHypoglycemic clamp studiesDiabetic pregnanciesGlucose counterregulationMaternal hypoglycemiaHypoglycemic stimulusEpinephrine releaseEpinephrine levelsMild hypoglycemiaBrisk responseNonfasting stateRisk factorsAwake ratsInsulin treatmentKetone levelsClamp studiesGlucose levelsNonfasted state
1991
Quantitation of Hepatic Glycogenolysis And Gluconeogenesis in Fasting Humans With 13C NMR
Rothman D, Magnusson I, Katz L, Shulman R, Shulman G. Quantitation of Hepatic Glycogenolysis And Gluconeogenesis in Fasting Humans With 13C NMR. Science 1991, 254: 573-576. PMID: 1948033, DOI: 10.1126/science.1948033.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
1980
Effect of hyperglycemia independent of changes in insulin or glucagon on lipolysis in the conscious dog
Shulman G, Williams P, Liljenquist J, Lacy W, Keller U, Cherrington A. Effect of hyperglycemia independent of changes in insulin or glucagon on lipolysis in the conscious dog. Metabolism 1980, 29: 317-320. PMID: 6103495, DOI: 10.1016/0026-0495(80)90004-9.Peer-Reviewed Original ResearchConceptsArterial plasma glucose concentrationDirect antilipolytic effectHepatic glycerol uptakeFree fatty acid concentrationsInfusion of somatostatinContinuous glucose infusionPlasma glucose concentrationBlood glycerol levelsHyperglycemia independentConscious dogsBlood glycerolFatty acid concentrationsPancreatic hormonesAntilipolytic effectGlucose infusionBasal levelsSignificant decreaseGlycerol levelsGlucose concentrationHyperglycemiaInfusionGlucagonInsulinFractional extraction
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 ResearchMeSH KeywordsAnimalsBlood GlucoseDogsFemaleGlucagonGlucoseInsulinLiverLiver GlycogenMaleSomatostatinConceptsNet 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