2022
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice
Gaspar R, Lyu K, Hubbard B, Leitner B, Luukkonen P, Hirabara S, Sakuma I, Nasiri A, Zhang D, Kahn M, Cline G, Pauli J, Perry R, Petersen K, Shulman G. Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice. Diabetologia 2022, 66: 567-578. PMID: 36456864, PMCID: PMC11194860, DOI: 10.1007/s00125-022-05838-8.Peer-Reviewed Original ResearchConceptsProtein kinase CsSubcellular compartmentsDistinct subcellular localisationMuscle insulin sensitivityMultiple subcellular compartmentsInsulin receptor kinaseNovel protein kinase CsActivation of PKCεSubcellular localisationPKCθ translocationReceptor kinasePlasma membraneSubcellular distributionTriacylglycerol contentCrucial pathwaysIntramuscular triacylglycerol contentRC miceDiacylglycerolConclusions/interpretationThese resultsPKCεPM compartmentPhosphorylationMuscle triacylglycerol contentSkeletal muscleRecent findings
2013
Role 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 Research
2012
The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats
Erion DM, Popov V, Hsiao JJ, Vatner D, Mitchell K, Yonemitsu S, Nagai Y, Kahn M, Gillum MP, Dong J, Murray SF, Manchem VP, Bhanot S, Cline GW, Shulman GI, Samuel VT. The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats. Endocrinology 2012, 154: 36-44. PMID: 23161873, PMCID: PMC3529388, DOI: 10.1210/en.2012-1725.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisResponse element-binding proteinCarbohydrate response element-binding proteinASO treatmentHepatic expressionNovo lipogenesisElement-binding proteinInsulin-stimulated peripheral glucose uptakeNonalcoholic fatty liver diseaseAntisense oligonucleotideMale Sprague-Dawley ratsHepatic de novo lipogenesisFructose-fed groupHepatic insulin responsivenessFatty liver diseaseFructose fed ratsPeripheral glucose uptakeHyperinsulinemic-euglycemic clampHigh-fat dietHepatic lipid contentHepatic triglyceride secretionHepatic insulin sensitivitySprague-Dawley ratsPlasma triglyceride concentrationsPlasma uric acid
2009
Prevention of Hepatic Steatosis and Hepatic Insulin Resistance by Knockdown of cAMP Response Element-Binding Protein
Erion DM, Ignatova ID, Yonemitsu S, Nagai Y, Chatterjee P, Weismann D, Hsiao JJ, Zhang D, Iwasaki T, Stark R, Flannery C, Kahn M, Carmean CM, Yu XX, Murray SF, Bhanot S, Monia BP, Cline GW, Samuel VT, Shulman GI. Prevention of Hepatic Steatosis and Hepatic Insulin Resistance by Knockdown of cAMP Response Element-Binding Protein. Cell Metabolism 2009, 10: 499-506. PMID: 19945407, PMCID: PMC2799933, DOI: 10.1016/j.cmet.2009.10.007.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceNonalcoholic fatty liver diseaseCAMP response element-binding proteinInsulin resistanceResponse element-binding proteinASO treatmentElement-binding proteinCREB expressionType 2 diabetes mellitusOb/ob miceFatty liver diseaseHepatic triglyceride contentPlasma glucose concentrationFed rat modelAttractive therapeutic targetAntisense oligonucleotideDiabetes mellitusLiver diseaseZDF ratsHepatic steatosisOb micePostprandial hyperglycemiaPlasma cholesterolRat modelTriglyceride concentrationsSensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Expression
Estall JL, Kahn M, Cooper MP, Fisher FM, Wu MK, Laznik D, Qu L, Cohen DE, Shulman GI, Spiegelman BM. Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Expression. Diabetes 2009, 58: 1499-1508. PMID: 19366863, PMCID: PMC2699879, DOI: 10.2337/db08-1571.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBlood GlucoseBody CompositionCell Culture TechniquesCrosses, GeneticFatty LiverFemaleGene Expression RegulationHepatocytesHomeostasisInsulinInsulin ResistanceIntegrasesKetonesLipidsLiverMiceMice, TransgenicPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRNA, Small InterferingTrans-ActivatorsTranscription FactorsTriglyceridesConceptsPGC-1alpha levelsCre/lox systemExpression of genesKey metabolic enzymesKey metabolic pathwaysPGC-1alpha activityPGC-1alpha expressionPeroxisome proliferator-activated receptor gamma coactivatorReceptor γ coactivatorLipid metabolismProliferator-activated receptor gamma coactivatorComplete genetic ablationTranscriptional coactivatorNutrient deprivationReceptor gamma coactivatorPGC-1alphaFatty acid oxidationOxidative phosphorylationMetabolic enzymesLox systemCoactivatorLipid homeostasisMetabolic pathwaysGenetic ablationGenetic alterations
2007
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance*
Choi CS, Savage DB, Kulkarni A, Yu XX, Liu ZX, Morino K, Kim S, Distefano A, Samuel VT, Neschen S, Zhang D, Wang A, Zhang XM, Kahn M, Cline GW, Pandey SK, Geisler JG, Bhanot S, Monia BP, Shulman GI. Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance*. Journal Of Biological Chemistry 2007, 282: 22678-22688. PMID: 17526931, DOI: 10.1074/jbc.m704213200.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseHepatic insulin resistanceProtein kinase C epsilon activationInsulin resistanceASO treatmentFat-induced hepatic insulin resistanceDiet-induced nonalcoholic fatty liver diseaseDiacylglycerol acyltransferase 2Epsilon activationHigh fat-fed ratsTriglyceride synthesisFatty liver diseaseType 2 diabetesHepatic fatty acid oxidationHepatic insulin sensitivityFat-fed ratsFatty acid oxidationHepatic diacylglycerol contentLiver diseaseHepatic lipidsHepatic steatosisControl ratsInsulin sensitivityPharmacological reductionParadoxical reduction