2019
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production
Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesMetabolic control pointPhosphorylation sitesNuclear retentionCDK activityPKL activityDays high-fat dietKinase phosphorylationImportant enzymePyruvate kinaseHigh-fat dietS113KinaseEnzyme kineticsPhosphorylationAdditional control pointsRegulationGlucose productionHepatic glucose productionInsulin resistanceGlycolysisEnzymePKAPathwayActivity
2014
The emerging role of oestrogen-related receptor γ as a regulator of energy metabolism
Samuel VT. The emerging role of oestrogen-related receptor γ as a regulator of energy metabolism. Diabetologia 2014, 57: 2440-2443. PMID: 25257097, PMCID: PMC4488899, DOI: 10.1007/s00125-014-3377-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGluconeogenesisInsulinLiverProto-Oncogene Proteins c-aktReceptors, EstrogenSignal Transduction
2013
Targeting Pyruvate Carboxylase Reduces Gluconeogenesis and Adiposity and Improves Insulin Resistance
Kumashiro N, Beddow SA, Vatner DF, Majumdar SK, Cantley JL, Guebre-Egziabher F, Fat I, Guigni B, Jurczak MJ, Birkenfeld AL, Kahn M, Perler BK, Puchowicz MA, Manchem VP, Bhanot S, Still CD, Gerhard GS, Petersen KF, Cline GW, Shulman GI, Samuel VT. Targeting Pyruvate Carboxylase Reduces Gluconeogenesis and Adiposity and Improves Insulin Resistance. Diabetes 2013, 62: 2183-2194. PMID: 23423574, PMCID: PMC3712050, DOI: 10.2337/db12-1311.Peer-Reviewed Original ResearchConceptsPyruvate carboxylaseAntisense oligonucleotideHepatocyte fatty acid oxidationInsulin resistanceNonalcoholic fatty liver diseaseZucker diabetic fatty ratsHigh fat-fed ratsFatty liver diseaseLiver biopsy specimensDiabetic fatty ratsPlasma lipid concentrationsType 2 diabetesHepatic insulin sensitivityHuman liver biopsy specimensEndogenous glucose productionHepatic insulin resistancePlasma glucose concentrationPotential therapeutic approachSpecific antisense oligonucleotideFat-fed ratsCarboxylaseFatty acid oxidationDe novo fatty acid synthesisLiver diseaseTissue-specific inhibitionThyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways
Vatner DF, Weismann D, Beddow SA, Kumashiro N, Erion DM, Liao XH, Grover GJ, Webb P, Phillips KJ, Weiss RE, Bogan JS, Baxter J, Shulman GI, Samuel VT. Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways. AJP Endocrinology And Metabolism 2013, 305: e89-e100. PMID: 23651850, PMCID: PMC3725564, DOI: 10.1152/ajpendo.00573.2012.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnilidesAnimalsDietary FatsFatty LiverGene ExpressionGluconeogenesisGlucose Transporter Type 4HyperglycemiaHyperinsulinismInsulin ResistanceMaleMuscle, SkeletalNon-alcoholic Fatty Liver DiseasePhenolsRatsRats, Sprague-DawleySignal TransductionThyroid Hormone Receptors betaTriglyceridesConceptsEndogenous glucose productionHepatic insulin sensitivityInsulin sensitivityHepatic steatosisFat-fed ratsInsulin-stimulated peripheral glucose disposalTRβ agonistsInsulin-stimulated skeletal muscle glucose uptakePotent lipid-lowering drugsNonalcoholic fatty liver diseaseWhite adipose tissue lipolysisMale Sprague-Dawley ratsSkeletal muscle glucose uptakeGC-1 treatmentPeripheral glucose disposalFatty liver diseaseImpairs insulin sensitivityLipid-lowering drugsHepatic triglyceride contentAdipose tissue lipolysisMuscle glucose uptakeSprague-Dawley ratsHepatic insulin resistanceSkeletal muscle insulinPotential adverse effects
2009
Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes
Samuel VT, Beddow SA, Iwasaki T, Zhang XM, Chu X, Still CD, Gerhard GS, Shulman GI. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 12121-12126. PMID: 19587243, PMCID: PMC2707270, DOI: 10.1073/pnas.0812547106.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsDiabetes Mellitus, Type 2Dietary FatsFastingFeeding BehaviorFemaleGene Expression Regulation, EnzymologicGluconeogenesisGlucose-6-PhosphataseHumansHyperglycemiaHyperinsulinismInsulin Infusion SystemsLiverMaleMiddle AgedPhosphoenolpyruvate Carboxykinase (ATP)RatsRats, Sprague-DawleyStreptozocinConceptsHigh-fat feedingEndogenous glucose productionHFF ratsExpression of PEPCKHepatic expressionType 2 diabetes mellitusBeta-cell compensationBeta-cell responseFirst rat modelPortal vein infusionLiver biopsy samplesHigher plasma glucosePhosphoenolpyruvate carboxykinaseBariatric surgeryT2DM patientsDiabetes mellitusInsulin resistancePlasma insulinPlasma glucosePortal infusionRat modelRodent modelsVein infusionHyperglycemiaKey gluconeogenic enzymes