2008
N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake
Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake. Cell 2008, 135: 813-824. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.Peer-Reviewed Original ResearchConceptsFood intakeInhibits food intakeTreatment of obesityNovel therapeutic targetCentral nervous systemUnknown physiological significanceFat ingestionCirculating factorsN-acylphosphatidylethanolaminePlasma lipidsIntracerebroventricular infusionPhysiologic dosesSystemic administrationTherapeutic targetBody weightNervous systemIngested fatSmall intestineIntakeTaste aversionInfusionPhysiological significanceNanomolar amountsObesityHypothalamus
2001
Prevention of fat-induced insulin resistance by salicylate
Kim J, Kim Y, Fillmore J, Chen Y, Moore I, Lee J, Yuan M, Li Z, Karin M, Perret P, Shoelson S, Shulman G. Prevention of fat-induced insulin resistance by salicylate. Journal Of Clinical Investigation 2001, 108: 437-446. PMID: 11489937, PMCID: PMC209353, DOI: 10.1172/jci11559.Peer-Reviewed Original ResearchConceptsType 2 diabetesLipid infusionInsulin resistanceGlucose uptakeInsulin actionWhole-body glucose uptakeFat-induced insulin resistanceSkeletal muscleHigh-dose salicylatesHyperinsulinemic-euglycemic clampWild-type miceInsulin-stimulated glucose uptakeSkeletal muscle insulinIRS-1-associated PISerine kinase cascadeLipid-induced effectsAwake ratsAwake miceKnockout miceMuscle insulinInfusionTherapeutic agentsSalicylate actionKinase cascadeIKK betaStimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans
Petersen K, Laurent D, Yu C, Cline G, Shulman G. Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans. Diabetes 2001, 50: 1263-1268. PMID: 11375325, DOI: 10.2337/diabetes.50.6.1263.Peer-Reviewed Original ResearchConceptsNet hepatic glycogen synthesisHepatic glycogen synthesisGlycogen synthesisSynthase fluxInfusion of fructoseLow-dose infusionType 2 diabetesEuglycemic hyperinsulinemic conditionsPotential therapeutic valueHepatic glycogen metabolismThreefold increaseFructose studiesEuglycemic hyperinsulinemiaHyperinsulinemic conditionsFructose infusionControl studyTherapeutic valueInfusionType 1Glucokinase activityGlycogen metabolismIndirect pathwaysStimulating effectInsulinStimulation
1999
Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR
Shen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cycleGlutamine cycleCerebral cortexMin/Rat cerebral cortexVivo 13C NMR spectraGlucose oxidation ratesHuman brainGlucose oxidationGlutamatergic activityRat modelTricarboxylic acid cycle rateParietal lobeHuman cortexCortexTime courseBrainGlutamine synthesisMajor metabolic fluxCycle rateTricarboxylic acid cycleHigh levelsInfusionRatsAcid cycleEffects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Dresner A, Laurent D, Marcucci M, Griffin M, Dufour S, Cline G, Slezak L, Andersen D, Hundal R, Rothman D, Petersen K, Shulman G. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity. Journal Of Clinical Investigation 1999, 103: 253-259. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/jci5001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultFatty Acids, NonesterifiedFemaleGlucoseGlucose Clamp TechniqueGlucose-6-PhosphateGlycerolGlycogenHumansHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismMagnetic Resonance SpectroscopyMaleMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsConceptsFree fatty acidsIRS-1-associated phosphatidylinositolLipid infusionInsulin resistanceGlycerol infusionPlasma free fatty acidsWhole-body glucose uptakeFive-hour infusionLipid/heparinHyperinsulinemic-euglycemic clampGlucose concentrationGlucose transportMuscle glycogen synthesisDiminished glucose transportMuscle biopsy samplesHuman skeletal muscleRate of insulinGlucose-6-phosphate concentrationFatty acidsHealthy subjectsBiopsy samplesInfusion studiesIdentical protocolInfusionIRS-1-associated PI
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 imagesMumol
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