2025
Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cellsThe Disposition Index in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes
Ismail H, Cuthbertson D, Galderisi A, Libman I, Jacobsen L, Moran A, Petrelli A, Atkinson M, Redondo M, Hannon T, Mather K, Sosenko J. The Disposition Index in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes. Diabetes 2025, 74: 1196-1204. PMID: 40173211, PMCID: PMC12185960, DOI: 10.2337/db24-1000.Peer-Reviewed Original ResearchConceptsFirst-phase insulin responseArea under the curveArea under the curve ratioType 1 diabetesB cell functionAutoantibody-positive individualsDPT-1Glucose tolerance testMatsuda indexDisposition indexRegression modelsDiabetic rangeAnalyzed cross-sectionallyTolerance testDiabetes Prevention Trial-Type 1Oral glucose tolerance testProgression to type 1 diabetesStudy participantsCox regression modelsAntibody-positive relativesInsulin secretionPrediction of T1DRisk scoreIntravenous glucose tolerance testMeasure of B-cell functionATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis
Slusher A, Santoro N, Vash-Margita A, Galderisi A, Hu P, Tokoglu F, Li Z, Tarabra E, Strober J, Vatner D, Shulman G, Caprio S. ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis. Journal Of Clinical Investigation 2025, 135: e184740. PMID: 40091831, PMCID: PMC11910223, DOI: 10.1172/jci184740.Peer-Reviewed Original ResearchConceptsHyperinsulinemic-euglycemic clampSubcutaneous adipose tissueInsulin resistanceAdipose triglyceride lipaseInsulin infusionOral glucose tolerance testAbdominal fat distributionGlucose tolerance testMeasuring abdominal fat distributionLower liver fatActivating adipose triglyceride lipaseMetabolic disease riskLiver fat contentEctopic lipid storageFUNDINGThis workAdipose tissue lipolysisInhibition of adipose tissue lipolysisSubcutaneous adipose tissue samplesFat distributionTolerance testInsulin exposureLiver fatInfusionGlycerol turnoverAdipose tissueA Glucose Fraction Independent of Insulin Secretion: Implications for Type 1 Diabetes Progression in Autoantibody-Positive Cohorts
Sosenko J, Cuthbertson D, Jacobsen L, Redondo M, Sims E, Ismail H, Herold K, Skyler J, Nathan B, Groups D. A Glucose Fraction Independent of Insulin Secretion: Implications for Type 1 Diabetes Progression in Autoantibody-Positive Cohorts. Diabetes Technology & Therapeutics 2025, 27: 179-186. PMID: 39757867, PMCID: PMC12084817, DOI: 10.1089/dia.2024.0422.Peer-Reviewed Original ResearchConceptsIndependent of insulin secretionArea under the curveAUC C-peptideAutoantibody-positive individualsC-peptideInsulin secretionAUC glucoseGlucose toleranceFirst-phase insulin responseDiabetes Prevention Trial-Type 1Type 1 diabetes progressionOral glucose tolerance test dataGlucose tolerance test dataPrediction of T1DImpaired glucose toleranceOral glucose toleranceType 1 diabetesDPT-1TrialNet PathwayIncreased glycemiaInsulin responseInverse correlationSecretionT1DLack of correlationThe Association Between Cost-Related Insulin Rationing and Health Care Utilization in U.S. Adults With Diabetes.
Borden C, Bakkila B, Nally L, Lipska K. The Association Between Cost-Related Insulin Rationing and Health Care Utilization in U.S. Adults With Diabetes. Diabetes Care 2025, 48: 400-404. PMID: 39746142, PMCID: PMC11870294, DOI: 10.2337/dc24-2117.Peer-Reviewed Original ResearchConceptsHealth care utilizationUrgent care visitsCare utilizationCare visitsU.S. adultsAssociated with health care utilizationNational Health Interview Survey respondentsAssociated with higher health care utilizationEmergency departmentHigher health care utilizationOdds of ED visitsRationing of health careCross-sectional studyNegative binomial regression modelsZero-inflated negative binomial regression modelsBinomial regression modelsHealth careED visitsSurvey weightsAge-stratifiedLogistic regressionSurvey respondentsVisitsRegression modelsAdultsDeterminants 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
Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study
Rajamoorthi A, Zheng H, Skowronski A, Zork N, Reddy U, Tung P, Kupsco A, Gallagher D, Salem R, Leibel R, LeDuc C, Thaker V. Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study. Diabetes Research And Clinical Practice 2024, 220: 111967. PMID: 39716665, PMCID: PMC11840794, DOI: 10.1016/j.diabres.2024.111967.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testC-peptide concentrationsC-peptideInsulin sensitivityCord bloodFollow-up studyInsulinogenic indexHOMA-IRCirculating C-peptide concentrationsCord blood C-peptideMaternal glucose concentrationsBlood C-peptideBMI z-scoreGlucose tolerance testPancreatic beta-cell developmentBeta-cell developmentGestational ageOGTT glucoseMaternal fastingAssociations of gestationalPubertal stageTolerance testInsulin resistanceZ-scoreMaternal covariatesInsulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial
Nadeau K, Arslanian S, Bacha F, Caprio S, Chao L, Farrell R, Hughan K, Rayas M, Tung M, Cross K, El ghormli L. Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial. Diabetologia 2024, 68: 676-687. PMID: 39706874, DOI: 10.1007/s00125-024-06327-w.Peer-Reviewed Original ResearchConceptsYouth-onset type 2 diabetesType 2 diabetesBeta cell functionRandomised clinical trialsVisceral adipose tissueMarkers of adiposityInsulin sensitivityInsulin clearanceSubcutaneous adipose tissueCell functionClinical trialsResponse to rosiglitazone treatmentDual-energy X-ray absorptiometryPersistently elevated blood glucose levelsMarkers of insulin sensitivityFasting blood testsX-ray absorptiometryFasting C-peptideNon-Hispanic black raceAdipose tissueResponse to treatmentCompensatory response to changesElevated blood glucose levelsNational Institute of DiabetesSecondary analysisLimitations in Achieving Glycemic Targets From CGM Data and Persistence of Severe Hypoglycemia in Adults With Type 1 Diabetes Regardless of Insulin Delivery Method
Laffel L, Sherr J, Liu J, Wolf W, Bispham J, Chapman K, Finan D, Titievsky L, Liu T, Hagan K, Gaglia J, Chandarana K, Pettus J, Bergenstal R. Limitations in Achieving Glycemic Targets From CGM Data and Persistence of Severe Hypoglycemia in Adults With Type 1 Diabetes Regardless of Insulin Delivery Method. Diabetes Care 2024, 48: 273-278. PMID: 39699995, PMCID: PMC11770157, DOI: 10.2337/dc24-1474.Peer-Reviewed Original ResearchDaily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity
Barbieri E, Bonet J, Fox D, Nelson R, Nelson M, Nelson L, Fernandez C, Van Name M, Samuels S, Caprio S, Sabati M, Galderisi A, Sherr J, Man C, Santoro N. Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity. Obesity 2024, 33: 116-124. PMID: 39658509, PMCID: PMC11666407, DOI: 10.1002/oby.24175.Peer-Reviewed Original ResearchConceptsIntrahepatic fat contentDaily glucose variabilityLiver proton density fat fractionProton density fat fractionGlucose variabilityInsulin sensitivityOral glucose tolerance testFat fractionInsulin secretionAssociated with insulin resistanceFirst-phase insulin secretionAssociated with 2-h glucoseGlucose tolerance testGlucose standard deviationMagnetic resonance imagingOral minimal modelCoefficient of variationBasal insulin secretionPediatric obesityPostprandial glucoseTolerance testCell sensitivityInsulin resistanceObesityResonance imagingThe use of automated insulin delivery around physical activity and exercise in type 1 diabetes: a position statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD)
Moser O, Zaharieva D, Adolfsson P, Battelino T, Bracken R, Buckingham B, Danne T, Davis E, Dovč K, Forlenza G, Gillard P, Hofer S, Hovorka R, Jacobs P, Mader J, Mathieu C, Nørgaard K, Oliver N, O’Neal D, Pemberton J, Rabasa-Lhoret R, Sherr J, Sourij H, Tauschmann M, Yardley J, Riddell M. The use of automated insulin delivery around physical activity and exercise in type 1 diabetes: a position statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD). Diabetologia 2024, 68: 255-280. PMID: 39653802, PMCID: PMC11732933, DOI: 10.1007/s00125-024-06308-z.Peer-Reviewed Original ResearchConceptsEuropean Association for the Study of DiabetesPhysical activityInternational Society for Pediatric and Adolescent DiabetesType 1 diabetesRegular physical activityPosition statementDiabetes careStudy of DiabetesClinical practice pointsResponse to PAManaged PAsEuropean Association for the StudyHealth benefitsAge groupsExerciseAdolescent DiabetesAutomated insulin deliveryDiabetesInsulin deliveryGlucose target rangeTherapy optionsClinical trialsDeliveryGlucose levelsCareAstrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
Ardanaz C, de la Cruz A, Minhas P, Hernández-Martín N, Pozo M, Valdecantos M, Valverde Á, Villa-Valverde P, Elizalde-Horcada M, Puerta E, Ramírez M, Ortega J, Urbiola A, Ederra C, Ariz M, Ortiz-de-Solórzano C, Fernández-Irigoyen J, Santamaría E, Karsenty G, Brüning J, Solas M. Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis. Science Advances 2024, 10: eadp1115. PMID: 39423276, PMCID: PMC11488540, DOI: 10.1126/sciadv.adp1115.Peer-Reviewed Original ResearchConceptsPeripheral glucose homeostasisBrain glucose metabolismGlucose metabolismAstrocytic glucose transporterGlucose homeostasisPeripheral glucose metabolismSystemic glucose metabolismATP releasePurinergic signalingBlood-borne glucoseBrain metabolismAstrocytesBrain energeticsInsulin signalingCognitive functionGlucose transportBrain functionMiceBrainGLUT1MetabolismHomeostasisObesityThe fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood
Jia Z, Qiu F, He Y, Chen H, Yang C, Liu H, Zheng T, Xu S, Wang S, Li Y. The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood. BMC Medicine 2024, 22: 429. PMID: 39379967, PMCID: PMC11462715, DOI: 10.1186/s12916-024-03629-z.Peer-Reviewed Original ResearchConceptsRestricted cubic splinesLeptin levelsMetabolic hormonesMetabolic healthDNA methylationRestricted cubic spline analysisProspective birth cohort studyDNA methylation ageMother-child pairsBirth cohort studyDNA copy numberFetal originMitochondrial DNA copy numberResultsThe linear regression analysisReal-time PCRCohort studyHorvath's epigenetic clockInsulin levelsInverse associationLeptinQuantitative real-time PCRInfinium MethylationEPIC BeadChipElectrochemiluminescence assayLinear regression analysisMetabolic statusIntestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage
Gong K, Xue C, Feng Z, Pan R, Wang M, Chen S, Chen Y, Guan Y, Dai L, Zhang S, Jiang L, Li L, Wang B, Yin Z, Ma L, Iwakiri Y, Tang J, Liao C, Chen H, Duan Y. Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage. Nature Communications 2024, 15: 6845. PMID: 39122737, PMCID: PMC11315690, DOI: 10.1038/s41467-024-51352-3.Peer-Reviewed Original ResearchConceptsEnteroendocrine cellsEndoplasmic reticulum (ER)-resident proteinGlucagon-like peptide 1Nogo-BEndoplasmic reticulumStimulate insulin secretionPotential therapeutic targetProglucagonGlucagon-like peptide 1 receptorInhibit glucagon secretionRegulatory processesIntestinal tractProglucagon fragmentInsulin secretionCleavageNogo-B knockoutTherapeutic targetPancreatic cellsPeptide 1Glucagon secretionCellsReticulonGolgiReticulon 4BInsulin resistancePopulation data evidence of interdependence of the limbs of hormonal feedback loops.
Fitzgerald S, Bean N, Falhammar H, Hoermann R, Korem Kohanim Y, Pohlabeln H, Grote Beverborg N, Tomassetti S. Population data evidence of interdependence of the limbs of hormonal feedback loops. Journal Of Endocrinology 2024, 262 PMID: 38727510, DOI: 10.1530/joe-23-0384.Peer-Reviewed Original ResearchFood perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver
Henschke S, Nolte H, Magoley J, Kleele T, Brandt C, Hausen A, Wunderlich C, Bauder C, Aschauer P, Manley S, Langer T, Wunderlich F, Brüning J. Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver. Science 2024, 384: 438-446. PMID: 38662831, DOI: 10.1126/science.adk1005.Peer-Reviewed Original ResearchConceptsMitochondrial fragmentationInsulin-stimulated suppression of hepatic glucose productionInduced mitochondrial fragmentationMitochondrial fission factorPro-opiomelanocortin (POMC)-expressing neuronsControl of hepatic glucose metabolismKnock-in mutationHepatic glucose metabolismFission factorMitochondrial dynamicsSerine 131Fragments in vitroNutrient availabilityKnock-in miceMitochondrial functionDynamic regulationHepatic glucose productionLiver mitochondriaSuppression of hepatic glucose productionMetabolic adaptationPhosphorylationNutritional stateGlucose productionIn vivoGlucose metabolismGlucose Regulation of β-Cell KATP Channels: It Is Time for a New Model!
Merrins M, Kibbey R. Glucose Regulation of β-Cell KATP Channels: It Is Time for a New Model! Diabetes 2024, 73: 856-863. PMID: 38768366, PMCID: PMC11109790, DOI: 10.2337/dbi23-0032.Peer-Reviewed Original ResearchConceptsB-cell metabolismInsulin secretionEfficiency of mitochondrial ATP productionModel of glucose-stimulated insulin secretionGlucose-stimulated insulin secretionMitochondrial ATP productionNADPH productionGenetic evidenceInitial insulin secretionATP productionGlycolytic enzymesOXPHOSPyruvate kinaseATP/ADP ratioHealthy B cellsKATP channel closureB cellsDiabetes pathophysiologyGlycolysisStoichiometric yieldKATP channelsBioenergeticsATP/ADPMembrane depolarizationMetabolismAltered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity
Slusher A, Nouws J, Tokoglu F, Vash‐Margita A, Matthews M, Fitch M, Shankaran M, Hellerstein M, Caprio S. Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity. Obesity 2024, 32: 593-602. PMID: 38410080, PMCID: PMC11034857, DOI: 10.1002/oby.23974.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueLiver fat contentInsulin resistanceInsulin sensitivityEctopic storage of lipidOral glucose tolerance testGluteal subcutaneous adipose tissueExtracellular matrix dynamicsMagnetic resonance imaging scansAdipose tissueBody fat distribution patternsFibrogenesis in vivoAdipocyte turnoverAssociated with insulin resistanceGlucose tolerance testFat distribution patternsWhole-body IRAdipose tissue insulin signalingTissue insulin signalingTolerance testGluteal fatImaging scansPathophysiological pathwaysAssociated with ratioObesityHousehold food insecurity is associated with greater autonomic dysfunction testing score in Latinos with type 2 diabetes
Bermúdez-Millán A, Feinn R, Lampert R, Pérez-Escamilla R, Segura-Pérez S, Wagner J. Household food insecurity is associated with greater autonomic dysfunction testing score in Latinos with type 2 diabetes. PLOS ONE 2024, 19: e0297681. PMID: 38394186, PMCID: PMC10889858, DOI: 10.1371/journal.pone.0297681.Peer-Reviewed Original ResearchConceptsDiastolic blood pressureAutonomic function testsAutonomic nervous systemType 2 diabetesHousehold food insecurityDysfunction indexFunction testsHigher diastolic blood pressureAverage diastolic blood pressureAssociated with ANS dysfunctionU.S. Household Food Security Survey ModuleHousehold Food Security Survey ModuleFood Security Survey ModuleBaseline supineFood insecuritySustained handgripBenefit health outcomesLow-income LatinosANS dysfunctionScore 0Improve food accessHandgrip testInsulin useBlood pressureHeart rate variabilityReal-World Evidence of Automated Insulin Delivery System Use
Considine E, Sherr J. Real-World Evidence of Automated Insulin Delivery System Use. Diabetes Technology & Therapeutics 2024, 26: 53-65. PMID: 38377315, PMCID: PMC10890954, DOI: 10.1089/dia.2023.0442.Peer-Reviewed Original ResearchConceptsGlucose management indicatorAid useRetrospective real-world studyMode of insulin deliveryGlycemic benefitsFollow-up periodTrial findingsFood and Drug AdministrationStandard of careReal-world studyInsulin deliveryType 1 diabetesNonpregnant individualsPivotal trialsRetrospective analysisPrimary outcomeHemoglobin A1cConclusion:</i></b>Drug AdministrationInclusion criteriaHbA1cGlycemic outcomesSystematic reviewResults:</i></b>Target range
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