Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes.
Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes.
复制标题
低血糖期间人脑谷氨酸浓度的变化：深入了解 1 型糖尿病低血糖相关自主神经衰竭的大脑适应。
DOI：
10.1038/jcbfm.2014.32
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Öz,Gülin
中科院分区：
文献类型：
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作者：
Terpstra,Melissa;Moheet,Amir;Kumar,Anjali;Eberly,LynnE;Seaquist,Elizabeth;Öz,Gülin
低血糖相关自主神经功能衰竭（HAAF）是一种1型糖尿病（T1 D）患者频繁发生低血糖时出现葡萄糖反调节缺陷并无法感知低血糖的疾病。脑内谷氨酸可能参与了HAAF的发病机制。本研究的目的是遵循人脑谷氨酸浓度在实验诱导的低血糖症的受试者和没有HAAF。1H磁共振波谱被用来跟踪枕叶皮层谷氨酸浓度在整个正葡萄糖钳夹，然后立即由低葡萄糖钳夹。研究了患有HAAF的T1 D患者与两个对照组的比较，即，无HAAF的T1 D患者和健康对照（每组n= 5）。在两个对照组中，在低血糖开始后，人脑谷氨酸浓度降低（P≥0.01），但HAAF患者的降低趋势较小，未达到显著性（P>0.05）。这些发现与HAAF中的代谢适应一致，以向大脑提供更高的葡萄糖和/或替代燃料，消除氧化谷氨酸的需要。在一项探索性分析中，我们检测到无HAAF对照组的T1 D患者对低血糖反应的额外代谢物变化，即天冬氨酸增加和乳酸减少。
Hypoglycemia-associated autonomic failure (HAAF) is a condition in which patients with type 1 diabetes (T1D) who experience frequent hypoglycemia develop defective glucose counter-regulation and become unable to sense hypoglycemia. Brain glutamate may be involved in the mechanism of HAAF. The goal of this study was to follow the human brain glutamate concentration during experimentally induced hypoglycemia in subjects with and without HAAF.1H magnetic resonance spectroscopy was used to track the occipital cortex glutamate concentration throughout a euglycemic clamp followed immediately by a hypoglycemic clamp. T1D patients with HAAF were studied in comparison to two control groups, i.e., T1D patients without HAAF and healthy controls (n= 5 per group). Human brain glutamate concentration decreased (P≥0.01) after the initiation of hypoglycemia in the two control groups, but a smaller trend toward a decrease in patients with HAAF did not reach significance (P>0.05). These findings are consistent with a metabolic adaptation in HAAF to provide higher glucose and/or alternative fuel to the brain, eliminating the need to oxidize glutamate. In an exploratory analysis, we detected additional metabolite changes in response to hypoglycemia in the T1D patient without HAAF control group, namely, increased aspartate and decreased lactate.