Measurement of glucose homeostasis in human brain by NMR

通过核磁共振测量人脑葡萄糖稳态

基本信息

批准号：
10312033
负责人：
Gulin Oz
金额：
$ 54.69万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10312033
关键词：
Acute Address Award Awareness Blood Glucose Brain Cerebral cortex Cerebrum Clinical Closure by clamp Data Development Diabetes Mellitus Disease Ensure Evaluation Exercise Exposure to Frequencies Fright Glucose Glutamates Goals Grant Hormones Human Hyperglycemia Hypoglycemia Hypothalamic structure Impairment Insulin-Dependent Diabetes Mellitus Investigation Kinetics Lead Learning Life Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measurement Measures Mediator of activation protein Metabolism Methodology Microvascular Dysfunction Modeling Neurotransmitters Oxides Patients Play Populations at Risk Positioning Attribute Protocols documentation Publishing Recurrence Reproducibility Risk Role Sleep Symptoms Syndrome Testing Time Up-Regulation Update Work actigraphy blood glucose regulation clinical risk data quality euglycemia experience experimental study frontal lobe gamma-Aminobutyric Acid glucose monitor glucose transport glycemic control healthy volunteer human model neurochemistry neuroimaging patient population preconditioning prevent response therapy design trend

项目摘要

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.

低血糖（IAH）的意识障碍，这是感知低血糖开始的能力（HG），通常并存，反调节激素反应（CRR）降低到Hg，三倍 1型糖尿病患者（T1D）患有潜在致命性严重低血糖症的风险。我们的长期术语目标仍然是确定复发性HG如何导致T1D中IAH的临床综合征。我们会在这里在暴露于实验性复发Hg之后，研究IAH的脑机制并检验以下假设，即T1D中复发Hg导致脑葡萄糖转运的上调以及谷氨酸能和GABA能的改变。我们将使用允许的MRS方法论在同一会议中评估脑皮质和下丘脑的评估，以同时评估大脑意识障碍和CRR受损的相关/调解人。高MR数据质量和可重复性将通过使用高现场MR扫描仪和我们在上一个赠款周期中取得的技术进步来确保（自动体素位置，实时体素跟踪，动态频率和垫片更新）。连续的葡萄糖监测和动作法将用于编年史葡萄糖变异性和活动/运动/睡眠在每个实验之前的几周中，以评估这些变量对IAH的影响。我们的具体目标是：目的1：测量在T1D（n = 50）之前和之后对低血糖的神经化学反应诱导IAH。包括谷氨酸，GABA和葡萄糖在内的神经化学谱将在额叶皮层，与先前神经影像学工作相关的区域，在下丘脑中，它调节 CRR，在7 Tesla的Eugllycemia和Hg期间，基线和经过重复的HG方案以鲁棒性诱导 T1D和NAH患者的IAH。目标2：在诱导IAH之前和之后，测量T1D（n = 50）中的脑葡萄糖转运。动力学葡萄糖转运的参数将在额叶皮层和下丘脑中使用高血糖测量基线和复发性汞后3特斯拉的夹具。这些实验将确定复发性HG是否改变了脑葡萄糖的可用性以及谷氨酸和GABA T1D中的音调以及这些大脑适应是否与钝的CRR的发展有关 T1D患者的症状减弱。此外，我们将学习血糖偏移和活动/睡眠会影响IAH的诱导。这些观察结果有望导致预防和在T1D中处理这种威胁生命的状况。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Revisiting Glycogen Content in the Human Brain.

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

The Impact of Diabetes on Cerebral Structure and Function.

DOI：
10.1097/psy.0000000000000207
发表时间：
2015-07
期刊：
Psychosomatic medicine
影响因子：
3.3
作者：
Seaquist ER
通讯作者：
Seaquist ER

In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7.

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

Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T.