The case for too little melatonin signalling in increased diabetes risk.
Genome-wide association studies have detected an association between type 2 diabetes risk and a non-coding SNP located in MTNR1B, the gene encoding melatonin receptor 2 (MT2). Melatonin regulates circadian rhythms and sleep and associates with metabolic disorders. However, the mechanisms underlying these actions are still unclear. Functional genomic, animal and clinical studies have not reached the same conclusions: while some studies have reported that decreased melatonin signalling increases type 2 diabetes risk, others have found the opposite. In this commentary, we have tried to provide an explanation for these contradictions and we suggest how the community may progress to reach a unified picture of the effect of melatonin and its signalling on type 2 diabetes.
European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Centre national de la recherche scientifique (CNRS), Unité mixte de recherche (UMR) 8199, University of Lille, 1 Rue du Professeur Calmette, B.P. 245, F-59019, Lille Cedex, France. amelie.bonnefond@inserm.fr.|Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 0NN, UK. amelie.bonnefond@inserm.fr.
Amélie
A
Bonnefond
European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Centre national de la recherche scientifique (CNRS), Unité mixte de recherche (UMR) 8199, University of Lille, 1 Rue du Professeur Calmette, B.P. 245, F-59019, Lille Cedex, France. pfroguel@ic.ac.uk.|Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 0NN, UK. pfroguel@ic.ac.uk.
Philippe
P
Froguel
D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D055106:Genome-Wide Association Study; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
C573871:MTNR1B protein, human; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
GWAS; Genome-wide association study; MTNR1B/MT2; Melatonin; Melatonin receptor; Pancreatic islets; Rare variants; SNP; Sequencing; eQTL