Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans.
Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans.
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DOI：
10.1016/j.metabol.2015.08.003
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Scheer FA
中科院分区：
文献类型：
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作者：
Garaulet M;Gómez-Abellán P;Rubio-Sastre P;Madrid JA;Saxena R;Scheer FA
常见的MTNR 1B遗传变异rs 10830963与2型糖尿病（T2 D）的风险增加有关。迄今为止，还没有实验研究测试在褪黑激素受体暴露于其配体期间MTNR 1B变体对人体葡萄糖代谢的影响。本研究的目的是研究与安慰剂相比，该MTNR 1B变体是否影响褪黑激素（5 mg）对通过口服葡萄糖耐量试验（OGTT; 75 g）在一天的不同时间（早晨和晚上）评估的葡萄糖耐量的作用。17名血糖正常的女性（24±6岁; BMI 23.0±3.3 kg/m2）完成了研究（11名风险等位基因携带者[CG]和6名非携带者[CC]）。褪黑激素对糖耐量的影响依赖于基因型。在早晨，褪黑激素（褪黑激素安慰剂）对基线以上葡萄糖曲线下面积（AUC）的影响在携带者和非携带者之间存在显著差异（P=0.036）。褪黑激素对携带者的影响是对非携带者的六倍。MTNR 1B SNP解释了褪黑激素对葡萄糖AUC影响的个体间差异的四分之一（26%）。而在夜间，褪黑素对携带者和非携带者血糖AUC的影响无显著性差异（P>0.05）。MTNR 1B rs 10830963风险变异消除了褪黑激素对葡萄糖耐量的影响，表明基因分型和个性化建议的重要性，特别是在褪黑激素水平升高时食用食物的人中。需要在弱势人群中进行大规模研究，以将这些结果转化为现实世界的临床相关建议。
The common MTNR1B genetic variant rs10830963 is associated with an increased risk of type 2 diabetes (T2D). To date, no experimental study has tested the effect of the MTNR1B variant on glucose metabolism in humans during exposure of the melatonin receptors to their ligand. The aim of this study was to investigate whether this MTNR1B variant influenced the effect of melatonin (5 mg) on glucose tolerance assessed by an oral glucose tolerance-test (OGTT; 75 g) at different times of the day (morning and evening) as compared to a placebo. Seventeen normoglycemic women (24±6 y; BMI 23.0±3.3 kg/m2) completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]). The effect of melatonin on glucose tolerance depended on the genotype. In the morning, the effect of melatonin (melatonin-placebo) on the glucose area-under-the-curve (AUC) above baseline differed significantly (P=0.036) between the carriers and noncarriers. This effect of melatonin on the carriers was six times as large as that on the noncarriers. The MTNR1B SNP explained over one-quarter (26%) of the inter-individual differences in the effect of melatonin on glucose AUC. However, in the evening, the effect of melatonin on glucose AUC of the carriers and noncarriers did not differ significantly (P>0.05). MTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose tolerance, suggesting the importance of genotyping and personalized recommendations, especially in people consuming food when melatonin levels are elevated. Large-scale studies in vulnerable populations are necessary to translate these results into real-world, clinically-relevant recommendations.