2023
1510-P: Lipid-Induced Renal Cortical Insulin Resistance Perturbs Gluconeogenic and Oxidative Metabolism via an sn-1,2-diacylglycerol-PKCe-Insulin Receptor Kinase Axis In Vivo
HUBBARD B, GASPAR R, ZHANG D, KAHN M, NASIRI A, SHULMAN G. 1510-P: Lipid-Induced Renal Cortical Insulin Resistance Perturbs Gluconeogenic and Oxidative Metabolism via an sn-1,2-diacylglycerol-PKCe-Insulin Receptor Kinase Axis In Vivo. Diabetes 2023, 72 DOI: 10.2337/db23-1510-p.Peer-Reviewed Original ResearchInsulin receptor kinasePyruvate carboxylaseHyperinsulinemic-euglycemic clampMitochondrial pyruvate oxidationInsulin resistanceOxidative metabolismMitochondrial pyruvate carboxylaseReceptor kinaseInhibitory phosphorylationAktS473 phosphorylationKinase axisChow fed miceImpairs insulinPyruvate oxidationKnockin micePhosphorylationKey targetFortress BiotechFed micePKCεDiacylglycerolRenal cortexHFDMetabolismBasal conditions
2021
Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation
Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, Shulman GI. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation. JCI Insight 2021, 6: e139946. PMID: 33411692, PMCID: PMC7934919, DOI: 10.1172/jci.insight.139946.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin actionAdipose tissue insulin resistanceTissue insulin resistanceWT control miceHyperinsulinemic-euglycemic clampShort-term HFDTissue insulin actionAdipose tissue insulin actionDiet-fed ratsPotential therapeutic targetHFD feedingControl miceInsulin sensitivityTherapeutic targetLipolysis suppressionImpairs insulinHFDPKCε activationGlucose uptakeΕ activationMiceDiacylglycerol accumulationRecent evidenceProtein kinase C