In vivo studies of brain glycogen in hypoglycemia

无意识低血糖是强化胰岛素治疗的一个并发症，常见于医源性胰岛素治疗后。 低血糖症。据报道，在健康的人类中，在发生一次 低血糖症。 “大脑检测低血糖浓度的机制是不确定的。大脑大约有3毫米 在中度低血糖时可作为燃料的糖原。在大多数组织中，糖原代谢是胰岛素-和 对葡萄糖敏感。因此，脑糖原提供了大脑碳水化合物代谢的一个方面，该方面对脑糖原的变化敏感 血糖动态平衡，如糖尿病患者所见。 本项目的目的是确定低血糖对脑糖原和葡萄糖代谢的影响以及潜在的 糖原代谢参与调节低血糖无意识。此外，我们将评估两国之间的关系 低血糖时的葡萄糖转运和脑血流量。 该项目的假设是：(A)脑糖原浓度和代谢受血糖和/或 体内胰岛素浓度。(B)脑糖原可以作为葡萄糖当量的储存库，用于延长 体内低血糖期间葡萄糖转运成为代谢限速和脑血流受阻的时间段 增加了。(C)在低血糖发作后，大脑储存了更多的脑糖原，从而使随后的更长和更深 低血糖是消耗脑糖原所必需的，这可能提供了一种导致低血糖无意识的机制。 具体目标如下：(1)区分急性脑葡萄糖浓度升高和脑葡萄糖浓度升高的影响 血浆胰岛素浓度对体内脑糖原代谢的影响。(2)测定脑超代偿程度 分级低血糖后的糖原，并确定脑糖原是葡萄糖单位的重要储存库 在低血糖期间。(3)确定脑糖原耗竭以及脑血流量的急剧增加在以下情况下被触发 脑部葡萄糖浓度接近己糖激酶的低千米。 这些目标将在大鼠大脑中使用定位的1H和13C核磁共振波谱和基于灌注的功能磁共振成像来实现。

Hypoglycemia unawareness is a complication of intensive insulin therapy often encountered after episodes of iatrogenic hypoglycemia. The associated blunting of counterregulation has been reported to occur in healthy humans after a single episode of hypoglycemia. "rhemechanisms 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, 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 purpose of this project is to determine the effect of hypoglycemia on brain glycogen and glucose metabolism and a potential involvement of glycogen metabolism in mediating hypoglycemia unawareness. In addition, we will assess the relationship between glucose transport and cerebral blood flow during hypoglycemia. The hypotheses of this project are (a) That brain glycogen concentration and metabolism are modulated by plasma glucose and/or insulin concentrations in vivo. (b) That brain glycogen can serve as a reservoir of glucose equivalents that are used for extended time periods during hypoglycemia in vivo when glucose transport becomes rate limiting for metabolism and cerebral blood flow is increased. (c) That following a hypoglycemic episode, the brain stores more brain glycogen such that longer and deeper subsequent hypoglycemia is necessary to deplete brain glycogen, which may provide a mechanism leading to hypoglycemia unawareness with the following specific aims: (1) To separate the effect of acutely elevated brain glucose concentrations from elevated plasma insulin concentrations on in vivo brain glycogen metabolism. (2) To determine the degree of supercompensation of brain glycogen following graded hypoglycemia and to establish that brain glycogen serves as a significant reservoir of glucosyl units during hypoglycemia. (3) To determine that depletion of brain glycogen as well as the acute increase in CBF is triggered when brain glucose concentrations approach the low Km of hexokinase. These aims will be achieved in rat brain using localized 1H and 13C NMR spectroscopy and perfusion-based fMRI.