NMR Measurements of Human Brain Glycogen Metabolism

描述（由申请人提供）：低血糖无意识是患者和正常人在发生医源性低血糖发作后进行强化胰岛素治疗的并发症。大脑检测低血糖浓度的机制尚不确定。大脑含有约3mm的糖原，可在中度低血糖时作为燃料。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，它对葡萄糖稳态的改变很敏感，比如糖尿病患者。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。到目前为止，脑糖原浓度和代谢还没有在活的人脑中测量。我们最近首次展示了可以使用非侵入性13C核磁共振波谱实现这一目标的方法。因此，本项目的目的是产生初步数据，并证明在人类中测量脑糖原的可行性。该项目的长期假设是正常情况下人脑糖原代谢非常缓慢，脑糖原浓度高于正常血糖状态下的游离脑糖浓度，具体目的是确定有意识的人脑中的脑糖原含量。这一目标将在人类大脑中使用局部13C核磁共振波谱来实现。

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.