Measurement of glucose homeostasis in human brain by NMR
Measurement of glucose homeostasis in human brain by NMR
批准号:
10312033
负责人:
Gulin Oz
金额:
$54.69万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-01-01 至 2023-12-31
关键词:
AcuteAddressAwardAwarenessBlood GlucoseBrainCerebral cortexCerebrumClinicalClosure by clampDataDevelopmentDiabetes MellitusDiseaseEnsureEvaluationExerciseExposure toFrequenciesFrightGlucoseGlutamatesGoalsGrantHormonesHumanHyperglycemiaHypoglycemiaHypothalamic structureImpairmentInsulin-Dependent Diabetes MellitusInvestigationKineticsLeadLearningLifeMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMeasurementMeasuresMediator of activation proteinMetabolismMethodologyMicrovascular DysfunctionModelingNeurotransmittersOxidesPatientsPlayPopulations at RiskPositioning AttributeProtocols documentationPublishingRecurrenceReproducibilityRiskRoleSleepSymptomsSyndromeTestingTimeUp-RegulationUpdateWorkactigraphyblood glucose regulationclinical riskdata qualityeuglycemiaexperienceexperimental studyfrontal lobegamma-Aminobutyric Acidglucose monitorglucose transportglycemic controlhealthy volunteerhuman modelneurochemistryneuroimagingpatient populationpreconditioningpreventresponsetherapy designtrend
中文摘要
低血糖意识受损(IAH),即对低血糖发作的感知能力减弱
英文摘要
Impaired awareness of hypoglycemia (IAH), which is a diminished ability to perceive the onset of hypoglycemia
(HG) and typically co-exists with a reduction in the counterregulatory hormone responses (CRR) to HG, triples
the risk of experiencing potentially fatal severe hypoglycemia for patients with type 1 diabetes (T1D). Our long-
term goal remains to identify how recurrent HG leads to the clinical syndrome of IAH in T1D. Here we will
study the cerebral mechanisms of IAH in the setting of T1D following exposure to experimental recurrent HG
and test the hypothesis that recurrent HG in T1D leads to an upregulation in brain glucose transport
and alterations in glutamatergic and GABAergic tone. We will use MRS methodology that permits
evaluation of cerebral cortex and hypothalamus in the same session to simultaneously evaluate the cerebral
correlates/mediators of impaired awareness and impaired CRR. High MR data quality and reproducibility will
be ensured by using high field MR scanners and technical advances we made during the last grant cycle
(automated voxel placement, real-time voxel tracking, dynamic frequency and shim updates). Continuous
glucose monitoring and actigraphy will be used to chronicle glucose variability and activity/exercise/sleep
during the weeks before each experiment to assess the impact of these variables on IAH. Our specific aims
are:
Aim 1: To measure the neurochemical response to hypoglycemia in T1D (N=50) before and after
induction of IAH. Neurochemical profiles including glutamate, GABA and glucose will be measured in the
frontal cortex, a region associated with IAH in prior neuroimaging work, and in hypothalamus, which regulates
CRR, during euglycemia and HG at 7 tesla, at baseline and after a recurrent HG protocol that robustly induces
IAH in patients with T1D and NAH.
Aim 2: To measure cerebral glucose transport in T1D (N=50) before and after induction of IAH. Kinetic
parameters for glucose transport will be measured in the frontal cortex and hypothalamus using hyperglycemic
clamps at 3 tesla at baseline and after recurrent HG.
These experiments will establish if recurrent HG alters cerebral glucose availability and glutamate and GABA
tone in T1D and if these cerebral adaptations are associated with the development of blunted CRR and
diminished symptoms in patients with T1D. In addition, we will learn how glycemic excursions and
activity/sleep impact the induction of IAH. These observations are expected to lead to new ways to prevent and
treat this life-threatening condition in T1D.
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DOI:
10.1007/s11064-015-1664-4
发表时间:
2015-12
期刊:
Neurochemical research
影响因子:
4.4
作者:
[Öz G, DiNuzzo M, Kumar A, Moheet A, Seaquist ER]
通讯作者:
Seaquist ER
Sweet and low: measuring brain glucose during hypoglycemia.
甜而低:测量低血糖期间的脑葡萄糖。
DOI:
10.2337/db12-0571
发表时间:
2012
期刊:
Diabetes
影响因子:
7.7
作者:
[Seaquist,ElizabethR, Öz,Gülin]
通讯作者:
Öz,Gülin
Diabetes: Does lactate sustain brain metabolism during hypoglycaemia?
糖尿病:低血糖期间乳酸能否维持大脑代谢?
DOI:
10.1038/nrendo.2013.104
发表时间:
2013
期刊:
Nature reviews. Endocrinology
影响因子:
--
作者:
[Seaquist,ElizabethR, Öz,Gülin]
通讯作者:
Öz,Gülin
Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes.
低血糖期间人脑谷氨酸浓度的变化:深入了解 1 型糖尿病低血糖相关自主神经衰竭的大脑适应。
DOI:
10.1038/jcbfm.2014.32
发表时间:
2014
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子:
--
作者:
[Terpstra,Melissa, Moheet,Amir, Kumar,Anjali, Eberly,LynnE, Seaquist,Elizabeth, Öz,Gülin]
通讯作者:
Öz,Gülin
DOI:
10.1002/mds.26181
发表时间:
2015-04-15
期刊:
MOVEMENT DISORDERS
影响因子:
8.6
作者:
[Adanyeguh, Isaac M., Henry, Pierre-Gilles, Nguyen, Tra M., Rinaldi, Daisy, Jauffret, Celine, Valabregue, Romain, Emir, Uzay E., Deelchand, Dinesh K., Brice, Alexis, Eberly, Lynn E., Oez, Guelin, Durr, Alexandra, Mochel, Fanny]
通讯作者:
Mochel, Fanny
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7th Ataxia Investigators Meeting, From Bench to Bedside: Entering a New Era of Ataxia Therapies
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批准号:9471485
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项目类别:
-
资助金额:$1.0万
-
财政年份:2017
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负责人:Gulin Oz
-
依托单位:
Partnership for Magnetic Resonance Spectroscopy Biomarker Development
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批准号:9134877
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项目类别:
-
资助金额:$64.53万
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财政年份:2015
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负责人:Gulin Oz
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依托单位:
Partnership for Magnetic Resonance Spectroscopy Biomarker Development
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批准号:9269280
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项目类别:
-
资助金额:$65.25万
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财政年份:2015
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负责人:Gulin Oz
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依托单位:
Partnership for Magnetic Resonance Spectroscopy Biomarker Development
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批准号:8929438
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项目类别:
-
资助金额:$69.06万
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财政年份:2015
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负责人:Gulin Oz
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依托单位:
NONINVASIVE QUANTITATION OF BIOCHEM CHANGESPARKINSONS
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批准号:8362816
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项目类别:
-
资助金额:$2.27万
-
财政年份:2011
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负责人:Gulin Oz
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依托单位:
NEUROCHEMICAL CORRELATES OF PATHOLOGY IN SPINOCEREBELLAR ATAXIAS
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批准号:8362815
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项目类别:
-
资助金额:$2.27万
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财政年份:2011
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负责人:Gulin Oz
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依托单位:
NON-INVASIVE QUANTITATION OF CELLU & BIOCHEM CHANGES IN SPINOCEREBELLAR ATAXIAS
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批准号:8362814
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项目类别:
-
资助金额:$2.27万
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财政年份:2011
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负责人:Gulin Oz
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依托单位:
NON-INVASIVE QUANTITATION OF CELLU & BIOCHEM CHANGES IN SPINOCEREBELLAR ATAXIAS
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批准号:8170419
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项目类别:
-
资助金额:$1.93万
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财政年份:2010
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负责人:Gulin Oz
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依托单位:
Magnetic Resonance Spectroscopy Biomarkers of Neurodegeneration
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批准号:8535224
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项目类别:
-
资助金额:$31.28万
-
财政年份:2010
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负责人:Gulin Oz
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依托单位:
Magnetic Resonance Spectroscopy Biomarkers of Neurodegeneration
-
批准号:8722634
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项目类别:
-
资助金额:$32.09万
-
财政年份:2010
-
负责人:Gulin Oz
-
依托单位:
Magnetic Resonance Spectroscopy Biomarkers of Neurodegeneration
-
批准号:8324308
-
项目类别:
-
资助金额:$32.41万
-
财政年份:2010
-
负责人:Gulin Oz
-
依托单位:
NONINVASIVE QUANTITATION OF BIOCHEM CHANGESPARKINSONS
-
批准号:8170421
-
项目类别:
-
资助金额:$1.93万
-
财政年份:2010
-
负责人:Gulin Oz
-
依托单位:
NEUROCHEMICAL CORRELATES OF PATHOLOGY IN SPINOCEREBELLAR ATAXIAS
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批准号:8170420
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项目类别:
-
资助金额:$1.93万
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财政年份:2010
-
负责人:Gulin Oz
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依托单位:
Magnetic Resonance Spectroscopy Biomarkers of Neurodegeneration
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批准号:8142031
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项目类别:
-
资助金额:$32.83万
-
财政年份:2010
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负责人:Gulin Oz
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依托单位:
Magnetic Resonance Spectroscopy Biomarkers of Neurodegeneration
-
批准号:8049311
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项目类别:
-
资助金额:$33.77万
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财政年份:2010
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负责人:Gulin Oz
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依托单位:
NON-INVASIVE QUANTITATION OF CELLU & BIOCHEM CHANGES IN SPINOCEREBELLAR ATAXIAS
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批准号:7954939
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项目类别:
-
资助金额:$1.28万
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财政年份:2009
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负责人:Gulin Oz
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依托单位:
NONINVASIVE QUANTITATION OF BIOCHEM CHANGESPARKINSONS
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批准号:7954941
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项目类别:
-
资助金额:$2.57万
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财政年份:2009
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负责人:Gulin Oz
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依托单位:
NEUROCHEMICAL CORRELATES OF PATHOLOGY IN SPINOCEREBELLAR ATAXIAS
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批准号:7954940
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项目类别:
-
资助金额:$2.57万
-
财政年份:2009
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负责人:Gulin Oz
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依托单位:
MAGNETIC RESONANCE SPECTROSCOPY IN ATAXIAS
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批准号:7954949
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项目类别:
-
资助金额:$2.57万
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财政年份:2009
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负责人:Gulin Oz
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依托单位:
MAGNETIC RESONANCE SPECTROSCOPY IN ATAXIAS
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批准号:7951678
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项目类别:
-
资助金额:$3.81万
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财政年份:2008
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负责人:Gulin Oz
-
依托单位:
海外基金