NMR MEASUREMENTS OF HUMAN BRAIN GLYCOGEN METABOLISM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 低血糖无意识是胰岛素强化治疗的一种并发症，常见于医源性低血糖发作后的患者和正常受试者。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13 C NMR光谱实现这一目标的方法。因此，本项目的目的是产生初步的数据，并证明测量人脑糖原的可行性。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。这一目标将实现在人脑中使用本地化的13 C NMR光谱，同时注入13 C标记的葡萄糖。葡萄糖输注和血液采样以及GCMS分析的管理需要GCRC的支持

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 noninvasive 13C NMR spectroscopy. Therefore, the aim of this project is to generate the preliminary data and demonstrate the feasibility of measurinig 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 gluose 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 while infusing 13C labeled glucose. Administration of the glucose infusions and blood sampling as well as GCMS analysis requires the support of the GCRC