NMDA receptor blockade by memantine does not prevent adaptation to recurrent hypoglycaemia in healthy men
NMDA receptor blockade by memantine does not prevent adaptation to recurrent hypoglycaemia in healthy men
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美金刚阻断 NMDA 受体不会阻止健康男性对反复低血糖的适应
作者：
Klement;Strube;Lehnert;Peters;Hallschmid
目的反复低血糖可导致低血糖症状和激素反调节反应的减轻。这一现象给糖尿病患者的治疗带来了严重的问题，但其潜在的神经内分泌机制尚不清楚。在动物实验结果的基础上，我们假设，逆调节衰减代表了一种依赖于突触长时程增强或抑制的基本适应性学习过程。如果是这样的话，应该通过阻断谷氨酰胺N-甲基-D-天冬氨酸受体来防止衰减。方法16名健康的年轻男性参加两种情况，间隔4 周。参与者在一种情况下接受了5 天(15 mg/天)的美金刚治疗，在另一种情况下接受了安慰剂治疗。给药3天后，受试者分别在第4天和第5天接受两次降糖钳夹治疗。我们评估了血液中反调节激素(皮质醇、促肾上腺皮质激素、肾上腺素、去甲肾上腺素、生长激素和高血糖素)的浓度，以及作为短期记忆指标的低血糖主观症状和单词列表回忆。结果与第一次低血糖相比，第三次低血糖后所有激素的反调节反应以及神经糖原和自主症状评分显示出明显的减弱(p <； 0.05)。美金刚拮抗NMDA受体可损害记忆功能，但不改变任何神经内分泌的反调节衰减指标(p>；0.17)。结论NMDA受体阻滞剂美金刚不能阻止反复低血糖对内分泌和症状性反调节反应的减弱。我们的结果不支持这样的观点，即对反复低血糖的适应依赖于NMDA受体介导的涉及长期增强或抑制的可塑性过程。
AimsRecurrent hypoglycaemia leads to an attenuation of hypoglycaemic symptoms and hormonal counterregulatory responses. This phenomenon poses a severe problem in the treatment of patients with diabetes mellitus, but the underlying neuroendocrine mechanisms are unclear. On the basis of animal experimental findings, we hypothesized that counterregulatory attenuation represents a basic adaptive learning process relying on synaptic long‐term potentiation or depression. If so, attenuation should be prevented by blocking glutamatergicN‐methyl‐d‐aspartate (NMDA) receptors.MethodsSixteen healthy young men participated in two conditions, separated by 4 weeks. Participants received the NMDA antagonist memantine over 5 days (15 mg/day) in one condition and placebo in the other one. After 3 days of drug administration, participants underwent two hypoglycaemic clamps on day 4 and another one on day 5. We assessed blood concentrations of counterregulatory hormones (cortisol, ACTH, epinephrine, norepinephrine, growth hormone and glucagon) as well as subjective symptoms of hypoglycaemia and word‐list recall as an indicator of short‐term memory.ResultsCounterregulatory responses of all hormones as well as neuroglycopenic and autonomic symptom ratings showed robust attenuation following the third as compared to the first hypoglycaemia (p < 0.05). NMDA receptor antagonization by memantine impaired memory function but did not alter any neuroendocrine measure of counterregulatory attenuation (p > 0.17).ConclusionsAttenuation of the endocrine as well as symptomatic counterregulatory response to recurrent hypoglycaemia is not prevented by the NMDA receptor blocker memantine. Our results do not support the view that adaptation to repeated hypoglycaemia relies on NMDA receptor‐mediated plastic processes involving long‐term potentiation or depression.
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1073/pnas.96.21.12085
发表时间：
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影响因子：
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作者：
Grunwald, T;Beck, H;Elger, CE
通讯作者：
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影响因子：
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作者：
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