NMR Measurements of Human Brain Glycogen Metabolism

描述(申请人提供)：低血糖意识不清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的并发症。大脑检测低血糖浓度的机制尚不确定。大脑含有大约3毫米糖原，在中度低血糖时可以作为燃料。在包括大脑在内的大多数组织中，糖原代谢是对胰岛素和葡萄糖敏感的。因此，脑糖原提供了大脑碳水化合物代谢的一个方面，对葡萄糖稳态的变化很敏感，例如在糖尿病患者中看到的变化。该项目的长期目标是探索低血糖对脑糖原代谢的影响，以及糖原代谢在调节低血糖意识中的潜在作用。到目前为止，还没有在活体人脑中测量到脑糖原浓度和代谢。我们最近首次展示了使用非侵入性13C核磁共振波谱实现这一目标的方法。因此，该项目的目的是产生初步数据，并论证测量人类脑糖原的可行性。该项目的长期假设是，在正常情况下，人脑糖原代谢非常缓慢，并且脑糖原浓度高于正常血糖的脑内游离葡萄糖浓度，专门目的是测定清醒人脑中的脑糖原含量。这一目标将通过在人脑中使用定位的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.