BRAIN TRANSPORT AND METABOLISM IN HYPOGLYCEMIA

低血糖，胰岛素治疗最常见的并发症 糖尿病，主要影响大脑。尽管如此，人们对此知之甚少 低血糖的长期后果或大脑如何适应它。 在初步研究中，使用了因植入物导致低血糖的大鼠 胰岛素瘤我们发现(1)这些大鼠会发展成特殊的神经学 症状(2)他们的大脑通过增加葡萄糖的提取和 (3)脑微血管加速代谢葡萄糖。 这项提案的总体目标是确定以下各项的基础 适应，它们如何保护大脑，以及当不足时，大自然 由此造成的损害。我们将检验以下假设：(1) 胰岛素瘤大鼠脑内葡萄糖摄取量增加 慢性低血糖，而不是通过胰岛素或其他肿瘤产品。(2) 慢性低血糖通过增加葡萄糖的含量来促进葡萄糖的提取 通过血脑屏障进行运输。如果是这样的话，它通过 增加大脑毛细血管中葡萄糖转运体的数量。(3) 当葡萄糖提取的适应性不足以维持 大脑的燃料需求，它要么使用其他燃料，要么减少它的 通过降低体温来满足燃料需求。(4)癫痫发作和其他 在适应的葡萄糖浓度较低时会出现神经症状 而不是在不适应的老鼠身上。相反，癫痫会慢性发作。 高血糖(糖尿病)大鼠，在较高的葡萄糖浓度。(5) 大脑的某些区域甚至容易受到慢性低血糖的影响 当整个大脑发生适应的时候。这些区域可以使用以下方法确定 2-脱氧葡萄糖技术和或通过分析神经行为变化 以及脑组织病理学。(6)数量上相似，但不太明显， 大鼠脑代谢、功能和病理发生改变 间歇性低血糖。 这些研究应该能让我们深入了解 正常人和糖尿病患者的低血糖及其改善 有助于预防它们的适应。

Hypoglycemia, the most common complication of insulin therapy in the diabetic, principally affects the brain. Despite this, little is known of the long term consequences of hypoglycemia or how the brain adapts to it. In preliminary studies using rats with hypoglycemia due to an implanted insulinoma we have found that (1) these rats develop specific neurological symptoms (2) their brains adapt by increasing the extraction of glucose and (3) their cerebral microvessels metabolize glucose at an accelerated rate. The overall objective of this proposal is to determine the basis for these adaptations, how they protect the brain, and when insufficient, the nature of the resultant damage. We will test the following hypotheses: (1) Glucose extraction by the brain of the insulinoma rat is increased by chronic hypoglycemia and not by insulin or other tumor products. (2) Chronic hypoglycemia enhances glucose extraction by increasing its transport across the blood-brain barrier. If so, it does this by increasing the number of glucose transporters in brain capillaries. (3) When the adaptation of glucose extraction is insufficient to maintain the fuel needs of the brain, it will either utilize other fuels or diminish its fuel requirements by lowering body temperature. (4) Seizures and other neurological symptoms will occur at lower glucose concentrations in adapted than in non-adapted rats. Conversely, seizures will occur in chronically hyperglycemic (diabetic) rats, at higher glucose concentrations. (5) Certain regions of the brain are vulnerable to chronic hypoglycemia even when overall brain adaptation occurs. These areas can be identified using the 2-deoxyglucose technique and or by analyzing neurobehavioral changes and brain histopathology. (6) Quantitatively similar, but less marked, alterations in brain metabolsim, function and pathology occur in rats with intermittent hypoglycemia. These studies should provide insights into the adverse effects of hypoglycemia in normal and diabetic subjects and the ameliorating adaptations that help to prevent them.