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

Investigating the polyol pathway in the human brain

研究人脑中的多元醇途径

基本信息

批准号：
9089213
负责人：
Janice Jin Hwang
金额：
$ 17.87万
依托单位：
YALE UNIVERSITY
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：
2016-08-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9089213
关键词：
Acute Adverse effects Affect Aldehyde Reductase Appetite Stimulants Attention Blood Glucose Brain Bypass Cardiovascular Diseases Cardiovascular system Cerebrospinal Fluid Chronic Complications of Diabetes Mellitus Diabetes Mellitus Diabetic Retinopathy Disease Environment Euglycemic Clamping Exposure to Fasting Fatty Liver Feeding behaviors Foundations Fructose Functional disorder Future Generations Glucose Glucose Clamp Glutathione Glycolysis Goals Hour Human Human body Hyperglycemia Image Impaired cognition Individual Infusion procedures Insulin Intravenous Kidney Diseases L-Iditol 2-Dehydrogenase Lead Link Magnetic Resonance Spectroscopy Measurement Measures Mediating Mediator of activation protein Mentored Patient-Oriented Research Career Development Award Metabolic Metabolism Methodology NMR Spectroscopy Neuraxis Neuropathy Non-Insulin-Dependent Diabetes Mellitus Oxidation-Reduction Oxidative Stress Pathogenesis Pathway interactions Patients Peripheral Peripheral Nervous System Diseases Physiological Physiology Plasma Play Prevalence Process Production Protocols documentation Research Research Personnel Retinal Diseases Role Severities Sorbitol Techniques Technology Testing Time Training Treatment Protocols Work base career combat diabetes management diabetic experience glycemic control healthy weight imaging modality improved inhibitor/antagonist insight medical schools metabolic abnormality assessment multidisciplinary neurovascular non-diabetic novel novel strategies polyol public health relevance response skills

项目摘要

DESCRIPTION (provided by applicant): The rising prevalence of type 2 diabetes mellitus (T2DM) amongst both younger and older individuals has led to increases in the lifetime exposure to T2DM. A growing body of evidence suggests that chronic hyperglycemia and T2DM leads to many adverse effects on brain function, particularly neurovascular disorders and cognitive impairment. However, the underlying mechanisms behind these associations remain unclear. The purpose of this application is to evaluate the role of the polyol pathway as a potential mediator of the CNS effects of hyperglycemia. The polyol pathway (glucose  sorbitol  fructose) is an alternate glucose pathway that is present throughout the human body, including the brain. In addition to fructose generation, polyol pathway activity has also been associated with increased oxidative stress and has been linked to the complications of diabetes including diabetic retinopathy, neuropathy and cardiovascular disease. However, the role of this pathway in the brain remains unclear. This K23 application will investigate the potential role of the polyol pathway in mediating the central nervous system effects of hyperglycemia by using nuclear magnetic resonance spectroscopy (MRS) which allows for the non-invasive measurements of brain metabolites as well as metabolic study methodology to alter peripheral glucose levels. The results from the physiology-based human studies in both healthy individuals as well as individuals with poorly controlled T2DM in this application will provide insights regarding whether the polyol pathway contributes to the endogenous production of fructose from glucose in the human brain as well as whether excessive activity through the pathway is associated with measures of increased oxidative stress in the brain. This research application will capitalize on the rich academic environment at Yale School of Medicine where a team of multidisciplinary independent investigators have joined together to utilize cutting edge imaging methodologies to investigate central questions in metabolism. Dr. Hwang, the Candidate for this K23 application, will gain important experience in the conduct and analysis of studies using MRS as well as metabolic techniques such as glucose clamp methodology. The findings from this study will lay the foundation for future studies targeting the polyol pathway to combat the central nervous system effects of diabetes and will help Dr. Hwang establish a long-term career as an independent investigator with an expertise in using state-of-the-art imaging modalities to understand the central nervous system effects of diabetes.