Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men
Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men
复制标题
通过输注香芹碱阻断 AMPA 受体信号传导不会影响健康男性低血糖的反调节
作者：
J. Klement;I. Pais;M. Hallschmid;C. Hubold;A. Knispel;K. Oltmanns;B. Schultes;J. Born;A. Peters
目的/假设谷氨酸途径被认为在低血糖的激素应激反应中起关键作用。在大鼠中，氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）受体上的谷氨酸信号有助于行为应激诱导的激素释放。我们假设，阻断AMPA受体的caroverine在健康的男性会削弱他们的感知神经低血糖症，从而减少激素的反调节以及低血糖的症状，作为一个模型的stress.MethodsIn平衡双盲研究，两次低血糖钳夹治疗（平均血糖2.4mmol/l，50分钟）在10名健康男性中在静脉内施用80 mg caroverine或安慰剂期间进行。我们评估了浓度的反调节激素以及主观症状相关的低血糖症。ResultsAMPA受体拮抗caroverine没有影响神经性低血糖症和自主性低血糖相关症状的看法（p > 0.39）。尽管如此，caroverine确实增加了基础和反调节胰高血糖素分泌（p < 0.002），并略微增加了反调节生长激素浓度（p = 0.07）。ACTH、皮质醇、肾上腺素（肾上腺素）和去甲肾上腺素（去甲肾上腺素）的反调节释放在不同条件下没有差异（所有条件下p > 0.11）。结论/解释在健康男性低血糖期间，通过caroverine输注拮抗AMPA受体信号传导未能减少甚至轻微放大反调节激素释放。与先前在大鼠中的发现的差异可能是由于不同的剂量或给药途径，并呼吁进一步研究AMPA受体信号传导在人类低血糖反调节中的作用。
Aims/hypothesisGlutamatergic pathways are assumed to play a critical role in the hormonal stress response to hypoglycaemia. In rats, glutamate signalling at the amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor contributes to hormone release induced by behavioural stressors. We hypothesised that blocking the AMPA receptor by caroverine in healthy men would impair their perception of neuroglycopenia and thereby diminish hormonal counter-regulation as well as symptoms of hypoglycaemia, as a model of stress.MethodsIn a balanced double-blind study, two hypoglycaemic clamp sessions (mean blood glucose 2.4 mmol/l for 50 min) were performed in ten healthy men during intravenous administration of 80 mg caroverine or placebo. We assessed concentrations of counter-regulatory hormones as well as subjective symptoms related to hypoglycaemia.ResultsAMPA receptor antagonisation by caroverine did not influence the perception of neuroglycopenic and autonomic hypoglycaemia-associated symptoms (p > 0.39 for all). Notwithstanding, caroverine did increase basal and counter-regulatory glucagon secretion (p < 0.002) and slightly enhanced counter-regulatory growth hormone concentrations (p = 0.07). Counter-regulatory release of ACTH, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine) did not differ between conditions (p > 0.11 for all).Conclusions/interpretationAntagonising AMPA receptor signalling by caroverine infusion failed to diminish and even slightly amplified counter-regulatory hormone release during hypoglycaemia in healthy men. The discrepancy with previous findings in rats may be due to different dosages or administration routes and calls for further investigations on the role of AMPA receptor signalling in hypoglycaemia counter-regulation in humans.
影响因子：
29
作者：
Tong, Qingchun;Ye, ChianPing;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.
影响因子：
29
作者：
Cabrera, Over;Jacques-Silva, M. Caroline;Berggren, Per-Olof
通讯作者：
Berggren, Per-Olof