Melatonin regulates circadian rhythm, but may also have effects on glucose homeostasis. A common G‐allele in the MTNR1B locus has been associated with an increased risk of type 2 diabetes (T2DM). We aimed to examine acute effects of high doses of melatonin on glucose metabolism with attention to MTNR1B genotype. Twenty men were examined in a double‐blinded, randomized crossover study on two nonconsecutive days with four doses of 10 mg oral melatonin or placebo. Insulin sensitivity and insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic‐euglycaemic clamp (HEC). Blood samples were drawn to determine the metabolic profile and MTNR1B rs10830963 genotype. Indirect calorimetry and blood pressure measurements were also performed. Insulin sensitivity index was significantly reduced on the melatonin day (P = .028) in the whole group and in homozygous carriers of the rs10830963 C‐allele (P = .041). Glucose during the IVGTT was unaffected, but there was a tendency towards lower insulin and C‐peptide levels in the first minutes after glucose administration in G‐allele carriers. Systolic blood pressure decreased and lipid oxidation increased significantly on the melatonin day in rs10830963 G‐allele carriers. Overall, our study reports that acute administration of melatonin in supra‐physiological doses may have a negative impact on insulin sensitivity.

中文翻译：

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褪黑激素的急性代谢作用——一项针对健康年轻男性的随机交叉研究

褪黑激素调节昼夜节律，但也可能对葡萄糖稳态产生影响。MTNR1B 中常见的 G 等位基因基因座与 2 型糖尿病 (T2DM) 的风险增加有关。我们旨在检查高剂量褪黑激素对葡萄糖代谢的急性影响，并关注 MTNR1B 基因型。在为期两天的双盲、随机交叉研究中，20 名男性接受了四剂 10 毫克口服褪黑激素或安慰剂的检查。通过静脉葡萄糖耐量试验（IVGTT）和高胰岛素-正常血糖钳夹（HEC）评估胰岛素敏感性和胰岛素分泌。抽取血样以确定代谢特征和 MTNR1B rs10830963 基因型。还进行了间接量热法和血压测量。胰岛素敏感性指数在褪黑激素日显着降低（P = .028) 在整个组和 rs10830963 C 等位基因的纯合子携带者中 ( P  = .041)。IVGTT 期间的葡萄糖不受影响，但在 G 等位基因携带者给予葡萄糖后的第一分钟内，胰岛素和 C 肽水平有降低的趋势。在 rs10830963 G 等位基因携带者的褪黑激素日，收缩压降低，脂质氧化显着增加。总体而言，我们的研究报告称，以超生理剂量急性施用褪黑激素可能会对胰岛素敏感性产生负面影响。