2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levels
2014
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014, 510: 542-546. PMID: 24847880, PMCID: PMC4074244, DOI: 10.1038/nature13270.Peer-Reviewed Original Research
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 levelsDiabetes
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 increaseLobeTissueNorepinephrineHypothalamusEpinephrine
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