2015
Second‐generation antisense oligonucleotides against β‐catenin protect mice against diet‐induced hepatic steatosis and hepatic and peripheral insulin resistance
Popov VB, Jornayvaz FR, Akgul EO, Kanda S, Jurczak MJ, Zhang D, Abudukadier A, Majumdar SK, Guigni B, Petersen KF, Manchem VP, Bhanot S, Shulman GI, Samuel VT. Second‐generation antisense oligonucleotides against β‐catenin protect mice against diet‐induced hepatic steatosis and hepatic and peripheral insulin resistance. The FASEB Journal 2015, 30: 1207-1217. PMID: 26644352, PMCID: PMC4750414, DOI: 10.1096/fj.15-271999.Peer-Reviewed Original ResearchConceptsHepatic steatosisInsulin resistanceAntisense oligonucleotideDiet-induced hepatic steatosisWhole-body glucose metabolismLipid-induced insulin resistanceMale C57BL/6 micePeripheral insulin resistanceHyperinsulinemic-euglycemic clampType 2 diabetesHepatic insulin sensitivityΒ-cateninHepatic lipid compositionWhite adipose tissueWnt/β-cateninΒ-catenin expressionMetabolic syndromeProtect miceC57BL/6 miceΒ-catenin mRNAFed miceHepatic triglyceridesInsulin sensitivityAwake miceGlucose metabolismInsulin-independent regulation of hepatic triglyceride synthesis by fatty acids
Vatner DF, Majumdar SK, Kumashiro N, Petersen MC, Rahimi Y, Gattu AK, Bears M, Camporez JP, Cline GW, Jurczak MJ, Samuel VT, Shulman GI. Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1143-1148. PMID: 25564660, PMCID: PMC4313795, DOI: 10.1073/pnas.1423952112.Peer-Reviewed Original Research
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 inhibitionRole of patatin‐like phospholipase domain‐containing 3 on lipid‐induced hepatic steatosis and insulin resistance in rats
Kumashiro N, Yoshimura T, Cantley JL, Majumdar SK, Guebre‐Egziabher F, Kursawe R, Vatner DF, Fat I, Kahn M, Erion DM, Zhang X, Zhang D, Manchem VP, Bhanot S, Gerhard GS, Petersen KF, Cline GW, Samuel VT, Shulman GI. Role of patatin‐like phospholipase domain‐containing 3 on lipid‐induced hepatic steatosis and insulin resistance in rats. Hepatology 2013, 57: 1763-1772. PMID: 23175050, PMCID: PMC3597437, DOI: 10.1002/hep.26170.Peer-Reviewed Original ResearchInvestigational anti-hyperglycemic agents: the future of type 2 diabetes therapy?
Majumdar SK, Inzucchi SE. Investigational anti-hyperglycemic agents: the future of type 2 diabetes therapy? Endocrine 2013, 44: 47-58. PMID: 23354728, DOI: 10.1007/s12020-013-9884-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsType 2 diabetesGlucose loweringCurrent therapiesFree Fatty Acid Receptor AgonistsNewer incretin-based therapiesGlucose cotransporter 2 inhibitorsDurable glycemic controlCotransporter 2 inhibitorsIncretin-based therapiesType 2 diabetes therapyIndividual patient characteristicsAcid receptor agonistsNew therapeutic classDiverse patient populationsMechanism of actionInsulin useComplex regimensPatient characteristicsGlycemic controlPatient populationType 1 inhibitorNatural courseReceptor agonistClinical trialsTreatment choice
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