Dongyan Zhang
Associate Research ScientistCards
About
Research
Publications
2026
2448-P: Short-Term Hypercaloric High-Fat Diet Feeding Induces White Adipocyte Insulin Resistance in Humans by Activation of the Protein Kinase cε Pathway
XOURAFA G, ZHANG D, GRANATA C, TRENKAMP S, SCHRAUWEN-HINDERLING V, SCHWEINITZER J, HUTTASCH M, PETERSEN K, SHULMAN G, KAHL S, RODEN M. 2448-P: Short-Term Hypercaloric High-Fat Diet Feeding Induces White Adipocyte Insulin Resistance in Humans by Activation of the Protein Kinase cε Pathway. Diabetes 2026, 75 DOI: 10.2337/db26-2448-p.Peer-Reviewed Original ResearchInsulin-stimulated Akt phosphorylationWhite adipose tissueEuropean Association for the StudyHigh-fat dietAkt phosphorylationWAT insulin sensitivityWhite adipose tissue biopsiesAdipocyte insulin resistanceHFD-induced IRHypercaloric high-fat dietInsulin resistancePhosphorylation pathwayHigh-fat diet feedingInsulin stimulationInsulin sensitivityAdipo-IRIsocaloric dietsParallel-group studyHepatic lipidsShort-term high-fat dietPro-inflammatory markersTranslocationWhole-body insulin sensitivityHyperinsulinemic-euglycemic clampPhosphorylationInsulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol
Hubbard B, Ma Y, Gaspar R, LaMoia T, Zhang D, Kahn M, Dufour S, Nasiri A, Shulman G. Insulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol. Nature Communications 2026 PMID: 42168167, DOI: 10.1038/s41467-026-73016-0.Peer-Reviewed Original ResearchHigh-fat dietRenal glucose productionSn-1,2-DAGElevated 6.5-foldImpaired suppression of endogenous glucose productionGlucose productionDysregulated glucose homeostasisMitochondrial metabolismInsulin signalingMitochondrial sourcesInsulin resistanceHigh-fat diet micePyruvate oxidationHFD-fedGlucose homeostasisKnockin miceGluconeogenesisPhosphorylationEndogenous glucose productionRenal gluconeogenesisGlycerolMiceImpaired suppressionMale micePyruvate
2025
Cideb knockdown in mice increases mitochondrial fat oxidation and reverses hepatic steatosis and insulin resistance by the plasma membrane sn-1,2-DAGs–PKCε–insulin receptor kinaseT1150 pathway
Zheng J, Gaspar R, Sakuma I, Hubbard B, Zhang D, Nasiri A, Kahn M, Perelis M, Samuel V, Petersen K, Shulman G. Cideb knockdown in mice increases mitochondrial fat oxidation and reverses hepatic steatosis and insulin resistance by the plasma membrane sn-1,2-DAGs–PKCε–insulin receptor kinaseT1150 pathway. Diabetologia 2025, 68: 2906-2920. PMID: 40908405, DOI: 10.1007/s00125-025-06539-8.Peer-Reviewed Original ResearchMitochondrial fat oxidationWhole-body energy expenditureTricarboxylic acidIn vivo rateHFD-induced hepatic steatosisHigh-fat dietHFD-induced insulin resistanceSteatotic liver diseaseAntisense oligonucleotidesHepatic lipogenesisHepatic mitochondrial oxidationHepatic insulin resistanceCidebHepatic steatosisComprehensive Lab Animal Monitoring SystemHigh-fat diet mouse modelInsulin resistanceMitochondrial oxidationMethodsC57BL/6J male miceRadio-labelled isotopesHyperinsulinaemic–euglycaemic clamp studiesKnockdownASO treatmentLipogenesisConclusions/interpretationThese findingsDeterminants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals
Pesta D, Anadol-Schmitz E, Sarabhai T, Kamp Y, Gancheva S, Trinks N, Zaharia O, Mastrototaro L, Lyu K, Habets I, Kamp-Bruls Y, Dewidar B, Weiss J, Schrauwen-Hinderling V, Zhang D, Gaspar R, Strassburger K, Kupriyanova Y, Al-Hasani H, Szendroedi J, Schrauwen P, Phielix E, Shulman G, Roden M. Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals. Science Advances 2025, 11: eadr8849. PMID: 39742483, PMCID: PMC11691647, DOI: 10.1126/sciadv.adr8849.Peer-Reviewed Original ResearchConceptsOverweight-to-obeseNormal weightEndurance-trained humansMuscle mitochondrial contentAthlete's paradoxTrained athletesExercise-trainedOverweight individualsAthletesObesity subtypesObservational studyIntramyocellular triglyceride accumulationInsulin sensitivityHigher insulin sensitivityMitochondrial contentIncreased insulin sensitivityMuscleFemale individualsIndividualsInsulin resistanceObesityMitochondrial partitioningIncreased calpainNPKC activityProtein kinase C
2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometryCeramide synthesis inhibitors prevent lipid-induced insulin resistance through the DAG-PKCε-insulin receptorT1150 phosphorylation pathway
Xu W, Zhang D, Ma Y, Gaspar R, Kahn M, Nasiri A, Murray S, Samuel V, Shulman G. Ceramide synthesis inhibitors prevent lipid-induced insulin resistance through the DAG-PKCε-insulin receptorT1150 phosphorylation pathway. Cell Reports 2024, 43: 114746. PMID: 39302831, DOI: 10.1016/j.celrep.2024.114746.Peer-Reviewed Original ResearchLipid-induced hepatic insulin resistanceHepatic insulin resistancePhosphorylation pathwayAntisense oligonucleotidesCeramide synthesis inhibitorsLipid-induced insulin resistanceMyriocin treatmentCeramide synthesisDihydroceramide desaturaseInsulin resistanceHepatic ceramideMyriocinCeramideCeramide contentInsulin-sensitizing effectsPhosphorylationHepatic insulin sensitivityPathwaySynthetic pathwayDES1Glucose productionSynthesis inhibitorDGAT2DesaturaseInhibitionCytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation
LaMoia T, Hubbard B, Guerra M, Nasiri A, Sakuma I, Kahn M, Zhang D, Goodman R, Nathanson M, Sancak Y, Perelis M, Mootha V, Shulman G. Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation. Cell Metabolism 2024, 36: 2329-2340.e4. PMID: 39153480, PMCID: PMC11446666, DOI: 10.1016/j.cmet.2024.07.016.Peer-Reviewed Original Research
2023
Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition
Sakuma I, Gaspar R, Luukkonen P, Kahn M, Zhang D, Zhang X, Murray S, Golla J, Vatner D, Samuel V, Petersen K, Shulman G. Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2312666120. PMID: 38127985, PMCID: PMC10756285, DOI: 10.1073/pnas.2312666120.Peer-Reviewed Original Research