权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Imaging Hepatic Gluconeogenesis with Hyperpolarized Dihydroxyacetone

使用超极化二羟基丙酮对肝脏糖异生进行成像

基本信息

批准号：
9975179
负责人：
MATTHEW E MERRITT
金额：
$ 34.26万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-30 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975179
关键词：
Affect Algorithms Back Bicarbonates Blood Glucose Bolus Infusion Brain C-Peptide C57BLKS/J Mouse Carbon Child Chronic Citric Acid Cycle Collaborations Consumption Depressed mood Detection Development Diabetes Mellitus Diagnosis Diagnostic Dihydroxyacetone Dose Effectiveness Embden Meyerhof pathway Epidemic Exhibits Fasting Fatty Acids Genetic Models Gluconeogenesis Glucose Glycerol Glycolysis Goals Gold Grant Hepatic Hexoses Image Institutes Insulin Insulin Resistance Intervention Intracellular Space Ionizing radiation Isotope Labeling Light Liver Magnetic Resonance Magnetic Resonance Imaging Measurement Measures Metabolism Metformin Methodology Methods Modeling Monitor Mus Nature Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Nuclear Pathology Pathway interactions Pharmacologic Substance Pharmacology Phosphoenolpyruvate Carboxylase Physiologic pulse Physiological Prediabetes syndrome Propionates Protocols documentation Pyruvate Rattus Regulation Research Rodent Model Safety Sum System Targeted Research Techniques Testing Time Tissues Tracer Trioses Vulnerable Populations base clinically relevant db/db mouse diabetic rat effectiveness measure experimental study feeding glucose output glucose production hepatic gluconeogenesis human imaging imaging agent imaging modality imaging system in vivo in vivo monitoring inorganic phosphate insight liver metabolism magnetic field metabolomics molecular imaging mouse model new technology oxidation pre-clinical pyruvate dehydrogenase reconstruction small molecule treatment planning treatment response

项目摘要

Project Summary Carbon-13 based dynamic nuclear polarization (DNP) experiments have shown tremendous potential for measuring glycolytic flux and pyruvate oxidation in living tissues and in vivo. However, the current stable of imaging agents cannot measure hepatic gluconeogenesis (GNG). We propose to develop [2- 13C]dihydroxyacetone (DHA) as an agent for measuring both GNG and hepatic glycolysis simultaneously. A ratio of three-carbon to hexose metabolites derived from DHA will provide a metric of net hepatic GNG. HP experiments will be compared to gold standard [U-13C]propionate/D2O based estimates of GNG and to targeted metabolomic profiles of glycolytic intermediates. We will measure GNG and glycolysis in three different rodent models. Aims 1 and 2 will target metabolism in the perfused liver of the C57BLKS/J mouse (control) and the well-accepted db/db model of diabetes and hepatic glucose overproduction. We will also assess the sensitivity of the method to treatment using a protocol based on metformin administration. Aim 3 of the grant transitions to in vivo experiments at 7 T that will be developed at the MD Anderson Center in collaboration with Dr. James Bankson. Dr. Bankson proposes to develop new constrained reconstruction algorithms that will enhance the localization of the 13C images, an extremely challenging issue for all hyperpolarized carbon-13 based imaging methods. We will use the Zucker (fa/fa) rat as a model of Type II diabetes. Subsequent experiments will be transferred back to UF for completion using the 11 T imaging system available through the National High Magnetic Field Lab at the McKnight Brain Institute. Relevance Diabetes is a worldwide epidemic that is projected to affect 300 million people worldwide by the year 2025. Methods for studying hepatic GNG are all based on tracer methodologies that require admittance to a general research center and administration of large amounts of isotopically labeled substrates. The method proposed here could be developed into a single exam that is integrated with standard magnetic resonance imaging protocols. We anticipate that the method proposed could be used to guide treatment plans for diabetes and determine the effectiveness of pharmacological interventions. Also, as a research target, the new method allows simultaneous measures of glycolysis and GNG. This observation is a fundamentally new insight into hepatic metabolism, and draws into light the nature of net hepatic GNG; it is the sum of the glycolytic and gluconeogenic activities within the tissue.

项目总结