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 inhibition
2011
Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism*
Birkenfeld AL, Lee HY, Majumdar S, Jurczak MJ, Camporez JP, Jornayvaz FR, Frederick DW, Guigni B, Kahn M, Zhang D, Weismann D, Arafat AM, Pfeiffer AF, Lieske S, Oyadomari S, Ron D, Samuel VT, Shulman GI. Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism*. Journal Of Biological Chemistry 2011, 286: 36163-36170. PMID: 21832042, PMCID: PMC3196114, DOI: 10.1074/jbc.m111.228817.Peer-Reviewed Original ResearchConceptsHepatic glucose productionInsulin sensitivityInsulin resistanceCaloric excessER stressHigh-fat diet-fed miceBasal plasma glucose concentrationsGlucose productionIGFBP-3 levelsHepatic ERPeripheral glucose metabolismTissue insulin sensitivityDiet-fed miceHepatic lipid accumulationHigh-fat dietHyperinsulinemic-euglycemic clampHepatic insulin sensitivityInfusion of insulinPlasma glucose concentrationEndoplasmic reticulum stress response pathwayEndoplasmic reticulum stressInsulin-stimulated muscleIGFBP-3Fat dietMuscle glucose