鼻内给予胰岛素与安慰剂对健康男性的非条件和条件作用：一项随机对照试验。
Unconditioned and conditioned effects of intranasally administered insulin vs placebo in healthy men: a randomised controlled trial.
机构信息
Department of Psychology, University of Osnabrueck, Seminarstrasse 20, D-49074 Osnabrueck, Germany.
出版信息
Diabetologia. 2011 Jun;54(6):1502-6. doi: 10.1007/s00125-011-2111-y. Epub 2011 Apr 2.
AIMS/HYPOTHESIS: In humans, the intranasal route allows insulin to reach the brain while maintaining peripheral euglycaemia. Our aims were to examine acute (unconditioned) effects of central insulin on normal-range blood glucose and hormones in men, and to find out whether the effects of intranasal insulin can be learnt via classical conditioning.
METHODS
In a randomised controlled trial, 32 healthy normal-weight men (mean age 24.2 [SEM 0.5], mean BMI 22.4 [0.3]) received a conditioned stimulus (CS) and six administrations of either soluble H-insulin 100 (20 U [0.2 ml]; group 1; n = 16) or vehicle (0.2 ml; group 2; n = 16) on day 1. The CS was the tarry smell of meta-cresol (used as a stabilising vehicle in many insulin preparations and placebos). On day 2, all participants received the CS and six administrations of placebo. Participants and experimenters were blinded to group assignment. Sixteen individuals were randomised to and analysed in each group. Participants were sequentially numbered for group allocation. The main outcome measures were blood glucose and insulin, expressed as cumulative difference-from-baseline changes.
RESULTS
While maintaining euglycaemia, intranasal insulin induced an increase of peripheral insulin on day 1 (group 1, 17.78 [21.88] pmol/l vs group 2, -10.24 [9.42] pmol/l), and also on day 2 when the CS was given with placebo (group 1, 12.53 [5.57] pmol/l vs group 2, -5.51 [6.16] pmol/l). Moreover, a moderate reduction of blood glucose on day 1 (group 1, -0.54 [0.36] mmol/l vs group 2, 0.58 [0.48] mmol/l) was obtained (all p values <0.05). There were no adverse side effects.
CONCLUSIONS/INTERPRETATION: The unconditioned blood glucose decrease on day 1 and the unconditioned and conditioned increases of peripheral insulin are indicative of brain-pancreas cross-talk. The conditionability of the hormonal responses reveals new applications for intranasal insulin.
TRIAL REGISTRATION
DRKS00000537 http://apps.who.int/trialsearch/
FUNDING
Deutsche Forschungsgemeinschaft DFG STO 323/1-1 and 1-2.
目的/假设：在人类中，鼻内途径允许胰岛素到达大脑，同时维持外周血糖正常。我们的目的是检查正常范围内的血糖和激素在男性中的急性（非条件）胰岛素的作用，以及确定鼻内胰岛素的作用是否可以通过经典条件作用来学习。
方法
在一项随机对照试验中，32 名健康的正常体重男性（平均年龄 24.2 [SEM 0.5]，平均 BMI 22.4 [0.3]）在第 1 天接受了条件刺激（CS）和六次可溶性 H-胰岛素 100（20 U [0.2 ml]；组 1；n = 16）或载体（0.2 ml；组 2；n = 16）的给药。CS 是煤酚的焦油味（用于许多胰岛素制剂和安慰剂的稳定剂）。第 2 天，所有参与者均接受 CS 和六次安慰剂给药。参与者和实验者对分组均不知情。每组随机分配并分析了 16 名个体。参与者按组分配进行编号。主要观察指标为血糖和胰岛素，以基线变化的累积差值表示。
结果
在维持血糖正常的情况下，鼻内胰岛素诱导第 1 天外周胰岛素升高（组 1，17.78 [21.88] pmol/l 与组 2，-10.24 [9.42] pmol/l），并且当 CS 与安慰剂一起给予时，第 2 天也会升高（组 1，12.53 [5.57] pmol/l 与组 2，-5.51 [6.16] pmol/l）。此外，第 1 天血糖也适度降低（组 1，-0.54 [0.36] mmol/l 与组 2，0.58 [0.48] mmol/l）（所有 p 值均 <0.05）。没有不良反应。
结论/解释：第 1 天的非条件性血糖下降以及外周胰岛素的非条件性和条件性升高表明了胰腺与大脑的交叉对话。激素反应的可条件性揭示了鼻内胰岛素的新应用。
试验注册
DRKS00000537 http://apps.who.int/trialsearch/
资助
德国研究基金会 DFG STO 323/1-1 和 1-2。
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