NMR Measurements of Human Brain Glycogen Metabolism

人脑糖原代谢的核磁共振测量

• 批准号: 6660353
• 负责人: ROLF GRUETTER
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6660353
• 关键词: awareness; bioimaging /biomedical imaging; blood chemistry; blood glucose; brain imaging /visualization /scanning; brain metabolism; clinical research; cognition disorders; glycogenesis; glycogenolysis; hormone regulation /control mechanism; human subject; hypoglycemia; insulin; nuclear magnetic resonance spectroscopy

DESCRIPTION (provided by applicant): Hypoglycemia unawareness is a complication of intensive insulin therapy often encountered in patients and normal subjects after episodes of iatrogenic hypoglycemia. The mechanisms by which the brain detects low blood sugar concentrations are uncertain. The brain contains approximately 3 mM glycogen that may serve as a fuel during moderate hypoglycemia. In most tissues, including the brain, glycogen metabolism is insulin- and glucose-sensitive. Brain glycogen thus provides an aspect of cerebral carbohydrate metabolism that is sensitive to alterations in glucose homeostasis such as those seen in diabetic patients. The long-term goal of this project is to explore the effect of hypoglycemia on brain glycogen metabolism and the potential role of glycogen metabolism in mediating hypoglycemia unawareness. To date, brain glycogen concentrations and metabolism have not been measured in the live human brain. We recently were the first to demonstrate methods that can achieve this goal using non-invasive 13C NMR spectroscopy. Therefore, the aim of this project is to generate the preliminary data and demonstrate the feasibility of measuring brain glycogen in humans. The long-term hypotheses of this project are that human brain glycogen metabolism under normal conditions is very slow and that the brain glycogen concentrations are higher than the euglycemic free brain glucose concentrations, with the specific aim to determine the brain glycogen content in the conscious human brain. This aim will be achieved in human brain using localized 13C NMR spectroscopy.

描述（由申请人提供）：低血糖无意识是患者和正常受试者在医源性低血糖发作后经常遇到的强化胰岛素治疗并发症。大脑检测低血糖浓度的机制尚不确定。大脑中含有大约3 mM的糖原，可在中度低血糖期间充当燃料。在大多数组织中，包括大脑，糖原代谢是胰岛素和葡萄糖敏感的。因此，脑糖原提供了脑碳水化合物代谢的一个方面，其对葡萄糖稳态的改变敏感，例如在糖尿病患者中所见的那些。本项目的长期目标是探讨低血糖对脑糖原代谢的影响以及糖原代谢在介导低血糖无意识中的潜在作用。迄今为止，尚未在活体人脑中测量脑糖原浓度和代谢。最近，我们首次展示了使用非侵入性13C NMR光谱实现这一目标的方法。因此，本项目的目的是生成初步数据，并证明测量人类脑糖原的可行性。该项目的长期假设是，正常条件下人脑糖原代谢非常缓慢，并且脑糖原浓度高于正常血糖游离脑葡萄糖浓度，具体目的是确定清醒人脑中的脑糖原含量。这一目标将在人脑中使用本地化的13 C NMR光谱学来实现。