Melatonin signalling and type 2 diabetes risk: too little, too much or just right?
Open accessAbstract
Of the associations of genetic variants with type 2 diabetes, the one of an SNP in an intron of the gene encoding the melatonin receptor 1B (MTNR1B) has been remarkably robust. Work from our group and others has provided support for a model where carriers of this risk G allele exhibit increased MTNR1B expression in islets of Langerhans. Most published studies to date favour that melatonin's action on the beta cell is inhibition of insulin secretion. Hence, our model proposes that this inhibitory effect of melatonin is exaggerated in carriers of the MTNR1B risk G allele. This would explain why this genetic association causes reduced insulin secretion and greater risk of future type 2 diabetes, as has been observed in numerous studies. Concurrently, another body of work has shown that rare MTNR1B alleles, which could perturb receptor function, also associate with type 2 diabetes. In this commentary, it is suggested that such apparently conflicting observations can be reconciled by the fact that non-coding (intronic; frequent) and coding (exonic; rare) alleles of MTNR1B give rise to different phenotypes. Thus, altered gene transcription may explain why SNPs, which do not alter coding sequences, exhibit cell-specific effects. In contrast, SNPs that change protein sequences are more likely to exert generalised effects since an altered protein will appear in all cells expressing the gene.
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The equilibrium hypothesis states that either exaggerated or dampened melatonin signaling in common and rare variant carriers, respectively, becomes detrimental for glucose homeostasis.
“These results are also in concordance with previous studies that support the”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [30]
Enhanced melatonin signaling in MTNR1B G risk allele carriers becomes detrimental for glucose homeostasis.
“(in this case, enhanced melatonin signaling in MTNR1B G risk allele carriers becomes detrimental for glucose homeostasis) (29,30).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [30]
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Cites
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Melatonin in type 2 diabetes mellitus and obesity
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- Authors
- Mulder, H.
- Affiliations
- Lund University (SE)
- Corresponding author
- Mulder, Hindrik
- ORCID
- Mulder, Hindrik
- Venue
- Diabetologia
- Published
- 2017-03-16
- Volume
- 60
- Issue
- 5
- Pages
- 826-829
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2595768508
- Cited by
- 33
- References
- 16
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 3
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Foundation for the Study of Diabetes
- Vetenskapsrådet
- Novo Nordisk Fonden (NNF16OC0020766, NNF17OC0027158)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- melatonin, type 2 diabetes risk, MTNR1B, single nucleotide polymorphisms, pancreatic beta cells, insulin secretion, rare alleles, intronic variants, gene expression, genetic association, cell type-specific gene expression
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Female, Humans, Male, Melatonin, Middle Aged, Signal Transduction, Sedentary Behavior
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