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Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go?

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Abstract

Purpose of Review

Type 2 diabetes (T2D) is a complex genetic metabolic disorder. T2D heritability has been estimated around 40–70%. In the last decade, exponential progress has been made in identifying T2D genetic determinants, through genome-wide association studies (GWAS). Among single-nucleotide polymorphisms mostly associated with T2D risk, rs10830963 is located in the MTNR1B gene, encoding one of the two receptors of melatonin, a neurohormone involved in circadian rhythms. Subsequent studies aiming to disentangle the role of MTNR1B in T2D pathophysiology led to controversies. In this review, we will tackle them and will try to give some directions to get a better view of MTNR1B contribution to T2D pathophysiology.

Recent Findings

Recent studies either based on genetic/genomic analyses, clinical/epidemiology data, functional analyses at rs10830963 locus, insulin secretion assays in response to melatonin (involving or not MTNR1B) or animal model analyses have led to strong controversies at each level of interpretation.

Summary

We discuss possible caveats in these studies and present ways to go beyond these issues, towards a better understanding of T2D molecular mechanisms, keeping in mind that melatonin is a versatile hormone and regulates many functions via its primary role in the body clock.

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Acknowledgements

Work related to melatonin in the authors’ laboratory is supported by the EASD/Janssen (‘Rising Star’, awarded to AB) and by the Agence Nationale de la Recherche (ANR-2011-BSV1-012-01 ‘MLT2D’ and ANR-2011-META “MELA-BETES”, awarded to AB and PF). AB is supported by Inserm.

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Authors and Affiliations

  1. CNRS UMR 8199. European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Pôle Recherche-1er - 1er étage Aile Ouest, 1 place de Verdun, 59045, Lille Cedex, France

    Amélie Bonnefond & Philippe Froguel

  2. Genomics of Common Disease, Imperial College London, London, W12 0NN, UK

    Philippe Froguel

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  1. Amélie Bonnefond
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Correspondence to Amélie Bonnefond.

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Amélie Bonnefond and Philippe Froguel declare that they have no conflict of interest.

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Bonnefond, A., Froguel, P. Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go?. Curr Diab Rep 17, 122 (2017). https://doi.org/10.1007/s11892-017-0957-1

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