Imaging beta cell function for metabolic surgery

代谢手术中β细胞功能成像

基本信息

批准号：
8856881
负责人：
Paul E Harris
金额：
$ 57.02万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8856881
关键词：
Abdomen Affect Amphetamines Anabolism Animal Model Asses Bariatrics Beta Cell Binding Biochemical Biochemistry Biological Blood Glucose Body Weight decreased Cell physiology Cell surface Cells Clinical Research Clinical Trials DRD2 gene Development Diabetes Mellitus Diagnostic Imaging Diet Discipline of Nuclear Medicine Disease Dopa Dopamine Duodenum Endocrine Environment Event Failure Family suidae Fasting GIPR gene Gastric Bypass Gastric Inhibitory Polypeptide Gastrointestinal tract structure Glucose Goals Human Hyperglycemia Image Imaging Techniques In Situ Ingestion Insulin Insulin Resistance Interdisciplinary Study Intestines Islets of Langerhans Kinetics Label Lead Ligands Location Maps Measurement Measures Mediating Metabolic Metabolism Methods Modeling Molecular Mus Non-Insulin-Dependent Diabetes Mellitus Operative Surgical Procedures Organ Pancreas Pathogenesis Patients Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Positron-Emission Tomography Prediabetes syndrome Primitive foregut structure Production Rattus Regulation Relative (related person)Research Series Serum Services Signal Transduction Source Stomach System Techniques Testing Time Tissues Tracer Tyrosine Upper digestive tract structure Vesicle Work arm autocrine bariatric surgery base blood glucose regulation cell type clinical application diabetes management glucagon-like peptide glucagon-like peptide 1 imaging modality improved in vivo inhibitor/antagonist insight insulin granule insulin secretagogues insulin secretion interest islet metabolomics minimally invasive molecular imaging novel novel diagnostics paracrine patient population pre-clinical public health relevance receptor response reuptake success uptake vesicular monoamine transporter

项目摘要

DESCRIPTION (provided by applicant): The objective of this proposal is to better understand the physiological and molecular mechanisms at work in the Roux-en-Y gastric bypass (RYGB) surgery mediated rapid reversal of the hyperglycemia associated with insulin resistance, prediabetes and T2DM. We propose a novel series of studies focused on the study of a recently recognized inhibitory circuit of glucose stimulated insulin secretion driven by dopamine (DA) stored in ß cell vesicles and the gut. We provide evidence that dopamine (DA) and Glucagon like peptide 1 (GLP-1) represent two opposing arms of a glucose stimulated insulin secretion (GSIS) regulatory system and hypothesize that DA represents the "anti incretin" hypothesized to explain the beneficial effects of bariatric surgery on T2DM. We propose to study these putative circuits using minimally invasive molecular imaging techniques in an animal model. Concurrently, we will characterize dopamine metabolism in the gut and pancreas under fasting and meal stimulated conditions, including a limited human clinical study of dopamine metabolism in a population of patients who have undergone RYGB surgery. The new information obtained from this hypothesis driven research may directly impact our understanding of: 1) the mechanisms underlying improved glucose homeostasis seen before weight loss following bariatric surgery, and 2) the regulation of glucose stimulated insulin secretion within islets. On a practical level, our studies may result in the development of novels methods to quantitatively asses in real time by imaging both beta cell function as well as mass. Such methods may have clinical application in the treatment and management of diabetes and/or for vetting new drugs aimed preserving or restoring beta cell function and mass in disease.

描述（由适用提供）：该提案的目的是更好地了解Roux-en-Y胃旁路（RYGB）手术中工作中的物理和分子机制介导的与胰岛素抵抗，预先拒绝和T2DM相关的高血糖的快速逆转。 We propose a novel series of studies focused on the study of a recently recognized inhibitory circuit of glucose stimulated insulin secretion driven by dopamine (DA) stored We provide evidence that dopamine (DA) and Glucagon like peptide 1 (GLP-1) represent two opposing arms of a glucose stimulated insulin secretion (GSIS) regulatory system and hypothesize that DA represents the "anti increasein" hypothesized to explain减肥手术对T2DM的有益作用。我们建议在动物模型中使用微创分子成像技术研究这些推定的电路。同时，我们将在禁食和进餐刺激的疾病下表征肠道和胰腺中多巴胺代谢，包括对种植RYGB手术的一群患者的多巴胺代谢的人类临床研究有限。从这项假设驱动的研究中获得的新信息可能直接影响我们对：1）减肥手术后体重减轻前发现的改善葡萄糖稳态的基础机制，以及2）调节胰岛内葡萄糖刺激的胰岛素分泌。在实际层面上，我们的研究可能会导致小说方法的发展，从而通过对β细胞功能和质量进行成像，从而实时定量驴。这种方法可能在糖尿病的治疗和治疗和/或审查针对保存或恢复疾病中β细胞功能和肿块的新药物的治疗和/或治疗中具有临床应用。