2024
Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes.
Petersen M, Yoshino M, Smith G, Gaspar R, Kahn M, Samovski D, Shulman G, Klein S. Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes. Diabetes 2024 PMID: 39264820, DOI: 10.2337/db24-0083.Peer-Reviewed Original ResearchMuscle insulin sensitivitySkeletal muscle insulin sensitivityType 2 diabetesEffects of weight lossInsulin sensitivityWeight lossWeight loss-induced improvementWhole-body insulin sensitivityObesityGlucose tracer infusionAssociated with changesHyperinsulinemic-euglycemic clamp procedureCeramide contentSn-1,2-DAGMuscleSmall molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease
Gaspar R, Sakuma I, Nasiri A, Hubbard B, LaMoia T, Leitner B, Tep S, Xi Y, Green E, Ullman J, Petersen K, Shulman G. Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease. AJP Endocrinology And Metabolism 2024, 327: e524-e532. PMID: 39171753, PMCID: PMC11482269, DOI: 10.1152/ajpendo.00175.2024.Peer-Reviewed Original ResearchGAA-KO miceMouse model of Pompe diseaseModel of Pompe diseasePompe diseaseMetabolic dysregulationRegular chowMouse modelSmall molecule inhibitionInsulin sensitivityReduced spontaneous activityGroups of male miceEnzyme acid alpha-glucosidaseProgressive muscle weaknessImprove metabolic dysregulationSynthase IWhole-body insulin sensitivityAcid alpha-glucosidaseImproved glucose toleranceIncreased AMPK phosphorylationWT miceAbnormal accumulation of glycogenGlycogen storage disorderMale miceSpontaneous activityImproved biomarkers1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway
ZHENG J, NASIRI A, GASPAR R, HUBBARD B, SAKUMA I, MA X, MURRAY S, PERELIS M, BARNES W, SAMUEL V, PETERSEN K, SHULMAN G. 1577-P: CIDEB Knockdown Promotes Increased Hepatic Mitochondrial Fat Oxidation and Reverses Hepatic Steatosis and Hepatic Insulin Resistance by the PKCε-Insulin Receptor Kinase Pathway. Diabetes 2024, 73 DOI: 10.2337/db24-1577-p.Peer-Reviewed Original ResearchReceptor kinase pathwaysMitochondrial fat oxidationHepatic insulin resistanceKinase pathwayExpression of cidebAmeliorated HFD-induced hepatic steatosisHFD-induced hepatic steatosisHFD-induced insulin resistanceSteatotic liver diseasePathogenesis of type 2 diabetesHepatic steatosisCidebHyperinsulinemic-euglycemic clamp studiesHepatic triglyceride accumulationInsulin resistanceReverse hepatic steatosisTriglyceride accumulationHepatic insulin sensitivityInsulin sensitivityPathwayHepatic expressionHigh-fatWhole-body insulin sensitivityLiver diseaseTranslocation
2023
FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity
Petersen M, Smith G, Yu J, Barve R, Yoshino J, Shulman G, Klein S. FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity. Journal Of The Endocrine Society 2023, 7: bvad114.043. PMCID: PMC10555440, DOI: 10.1210/jendso/bvad114.043.Peer-Reviewed Original ResearchAbdominal subcutaneous adipose tissueWhole-body insulin sensitivityInsulin sensitivityMUO groupMuscle ceramide contentCeramide contentAdipose tissueGreater whole-body insulin sensitivityPlasma C-peptide concentrationC-peptide concentrationsAdverse metabolic effectsSubcutaneous adipose tissueExpression of genesSkeletal muscle expressionMitochondrial content/functionHealthy obesityMitochondrial structure/functionSkeletal muscle diacylglycerolUnhealthy obesityExtracellular matrix remodelingExcess adiposityMHL groupMetabolic effectsMuscle diacylglycerolInsulin action191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice
EL-AGROUDY N, SCHUMANN T, KURZBACH A, SANCAR G, SANDFORTH L, HERRMANN C, SHULMAN G, BIRKENFELD A. 191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice. Diabetes 2023, 72 DOI: 10.2337/db23-191-or.Peer-Reviewed Original ResearchDb/db miceOb/obInsulin sensitivityDb miceMRNA expressionWhole-body insulin sensitivitySkeletal muscle insulin sensitivitySkeletal muscle insulin resistanceSkeletal musclePeripheral insulin sensitivityTreatment of T2D.Hyperinsulinemic-euglycemic clampLiver fat contentGlucose infusion rateMuscle insulin sensitivityMuscle insulin resistanceHepatic glucose productionHepatic mitochondrial functionWT littermate mice
2021
281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid Metabolism
GOEDEKE L, SON N, LAMOIA T, NASIRI A, KAHN M, ZHANG X, CLINE G, GOLDBERG I, SHULMAN G. 281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid Metabolism. Diabetes 2021, 70 DOI: 10.2337/db21-281-or.Peer-Reviewed Original ResearchFatty acid uptakeLong-chain fatty acid uptakeAcid uptakeEndothelial cell CD36EC-specific deletionDifferent cell typesInsulin-stimulated glucose uptakeLipid metabolismWhole-body glucose toleranceTransmembrane proteinTissue fatty acid uptakeWhole-body insulin sensitivityEndothelial cellsHepatic glucose productionCell typesInsulin sensitivityGlucose transportSystemic glucoseSkeletal muscleCD36Glucose uptakeWhole-body fat utilizationGlucose productionSynthase fluxNon-esterified fatty acid levels
2020
459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome
GOEDEKE L, ROTLLAN N, TOUSSAINT K, NASIRI A, ZHANG X, LEE J, ZHANG X, FERNÁNDEZ-HERNANDO C, SHULMAN G. 459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome. Diabetes 2020, 69 DOI: 10.2337/db20-459-p.Peer-Reviewed Original ResearchWhole-body insulin sensitivitySpouse/partnerInsulin sensitivityCardiovascular diseaseMetabolic syndromeAortic root plaque areaHigh fat-cholesterol dietLdlr-/- mouse modelTreatment of CVDEctopic lipid contentLDLR-/- micePeripheral insulin sensitivityNecrotic core areaType 2 diabetesAnti-atherogenic roleFibrous cap areaAdvisory PanelCRMP treatmentAttenuates AtherosclerosisCardiometabolic disordersFatty liverCholesterol dietInsulin resistanceNondiabetic individualsHepatic triglycerides
2019
Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis
Edmunds LR, Huckestein BR, Kahn M, Zhang D, Chu Y, Zhang Y, Wendell SG, Shulman GI, Jurczak MJ. Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis. Physiological Reports 2019, 7: e14281. PMID: 31724300, PMCID: PMC6854109, DOI: 10.14814/phy2.14281.Peer-Reviewed Original ResearchConceptsPark2 KO miceHepatic insulin sensitivityKO miceInsulin sensitivityInsulin resistanceShort-term HFD feedingDiet-induced hepatic insulin resistanceWhole-body insulin sensitivityPark2 knockout miceImproved hepatic insulin sensitivityDiet-induced obesityHigh-fat dietBioactive lipid speciesTumor necrosis factorHepatic insulin resistanceHepatic AMPK activationNegative energy balanceEndoplasmic reticulum stress responseRegular chowCytokine levelsHFD feedingReduced steatosisChronic HFDInterleukin-6Necrosis factorAnti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance
Camporez JP, Lyu K, Goldberg EL, Zhang D, Cline GW, Jurczak MJ, Dixit VD, Petersen KF, Shulman GI. Anti‐inflammatory effects of oestrogen mediate the sexual dimorphic response to lipid‐induced insulin resistance. The Journal Of Physiology 2019, 597: 3885-3903. PMID: 31206703, PMCID: PMC6876753, DOI: 10.1113/jp277270.Peer-Reviewed Original ResearchConceptsObesity-induced insulin resistanceHigh-fat dietEctopic lipid contentWhite adipose tissue lipolysisInsulin resistanceAdipose tissue lipolysisMale miceInsulin sensitivityFemale miceInsulin-stimulated suppressionWAT inflammationTissue lipolysisRodent studiesTumor necrosis factor αWhole-body insulin sensitivityLipid-induced insulin resistanceMetabolic homeostasisAge-matched menInterleukin-6 concentrationsSkeletal muscleAnti-inflammatory effectsType 2 diabetesInsulin-mediated suppressionSexual dimorphic responseNecrosis factor α
1999
Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study
Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Shulman G, Roden M. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999, 42: 113-116. PMID: 10027589, DOI: 10.1007/s001250051123.Peer-Reviewed Original ResearchConceptsIntramyocellular lipid concentrationsIntramyocellular lipid contentInsulin sensitivityLipid concentrationsPlasma non-esterified fatty acid concentrationsNon-esterified fatty acid concentrationsWhole-body insulin sensitivityNon-diabetic adultsNon-esterified fatty acidsBody insulin sensitivityNon-obese humansMuscle biopsy studiesCross-sectional analysisInsulin resistanceIntramuscular lipid contentBiopsy studiesClamp testFatty acid concentrationsLipid contentPlasma concentrationsSoleus muscleLinear regression analysisPmol/Inverse correlationM values