Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
J Pineal Res. 2021 Mar;70(2):e12706. doi: 10.1111/jpi.12706. Epub 2020 Dec 6.
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. Clinical trial registration number (clinicaltrial.gov): NCT03204877.
褪黑素调节昼夜节律，但也可能对葡萄糖稳态产生影响。MTNR1B 基因座的常见 G 等位基因与 2 型糖尿病（T2DM）的风险增加有关。我们旨在研究大剂量褪黑素对葡萄糖代谢的急性影响，并关注 MTNR1B 基因型。20 名男性在一项双盲、随机交叉研究中，在两天内连续服用四次 10mg 口服褪黑素或安慰剂，共进行了 20 次检查。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。采集血样以确定代谢谱和 MTNR1B rs10830963 基因型。还进行了间接测热法和血压测量。整个组和 rs10830963 C 等位基因纯合子携带者的胰岛素敏感性指数在褪黑素日显著降低（P=0.028）。IVGTT 期间的葡萄糖不受影响，但在葡萄糖给药后的最初几分钟，G 等位基因携带者的胰岛素和 C 肽水平有降低的趋势。在 rs10830963 G 等位基因携带者中，褪黑素日的收缩压降低和脂质氧化显著增加。总体而言，我们的研究报告表明，超生理剂量的褪黑素急性给药可能对胰岛素敏感性产生负面影响。临床试验注册号（clinicaltrial.gov）：NCT03204877。
