BRAIN TRANSPORT AND METABOLISM IN HYPOGLYCEMIA

低血糖是胰岛素治疗的最常见并发症， 糖尿病主要影响大脑 尽管如此， 低血糖的长期后果或大脑如何适应它。 在使用由于植入的低血糖症大鼠的初步研究中， 我们发现，（1）这些大鼠发展出特定的神经系统 症状（2）他们的大脑通过增加葡萄糖的提取来适应， (3)他们的大脑微血管以加速的速度代谢葡萄糖。 本建议的总体目标是确定这些建议的基础， 适应，它们如何保护大脑，当不足时，自然 造成的损害。 我们将检验以下假设：（1） 胰岛素瘤大鼠脑的葡萄糖提取增加， 慢性低血糖，而不是胰岛素或其他肿瘤产品。 （二） 慢性低血糖症通过增加葡萄糖的摄取来增强葡萄糖的摄取。 穿过血脑屏障。 如果是这样， 增加脑毛细血管中葡萄糖转运蛋白的数量。 （三） 当葡萄糖提取的适应不足以维持 大脑的燃料需求，它要么利用其他燃料，要么减少其 通过降低体温来满足燃料需求。 (4)癫痫和其他 适应性糖尿病患者在较低的葡萄糖浓度下会出现神经系统症状。 比不适应环境的老鼠要多。 相反，癫痫发作将发生在慢性 高血糖（糖尿病）大鼠，在较高的葡萄糖浓度。 （五） 大脑的某些区域容易受到慢性低血糖的影响， 当大脑整体适应发生时 这些区域可以使用 2-脱氧葡萄糖技术和/或通过分析神经行为变化 和脑组织病理学。 (6)数量相似，但不太明显， 脑代谢、功能和病理学的改变发生在具有以下特征的大鼠中： 间歇性低血糖 这些研究应该提供对不良影响的见解， 在正常和糖尿病受试者中的低血糖和改善 这些适应性变化有助于预防它们。

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.