The past decade has witnessed a revival of interest in the hormone melatonin, partly attributable to the discovery that genetic variation in MTNR1B - the melatonin receptor gene - is a risk factor for impaired fasting glucose and type 2 diabetes (T2D). Despite intensive investigation, there is considerable confusion and seemingly conflicting data on the metabolic effects of melatonin and MTNR1B variation, and disagreement on whether melatonin is metabolically beneficial or deleterious, a crucial issue for melatonin agonist/antagonist drug development and dosing time. We provide a conceptual framework - anchored in the dimension of 'time' - to reconcile paradoxical findings in the literature. We propose that the relative timing between elevated melatonin concentrations and glycemic challenge should be considered to better understand the mechanisms and therapeutic opportunities of melatonin signaling in glycemic health and disease.

中文翻译：

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褪黑激素对葡萄糖代谢的影响：是时候解开争议了

过去十年，人们对褪黑激素的兴趣重新燃起，部分原因是发现 MTNR1B（褪黑激素受体基因）的遗传变异是空腹血糖受损和 2 型糖尿病 (T2D) 的危险因素。尽管进行了深入的研究，但关于褪黑激素和 MTNR1B 变异的代谢影响仍存在相当多的混乱和看似相互矛盾的数据，并且对于褪黑激素是否对代谢有益或有害存在分歧，这是褪黑激素激动剂/拮抗剂药物开发和给药时间的关键问题。我们提供了一个概念框架——锚定在“时间”的维度——来调和文献中的矛盾发现。我们建议应考虑褪黑激素浓度升高与血糖挑战之间的相对时间，以更好地了解褪黑激素信号在血糖健康和疾病中的机制和治疗机会。