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Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion
Open accessAbstract
Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D.
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“the rs10830963 T2D risk variant is associated with impaired fasting glucose and measures of decreased insulin secretion in daytime OGTT assessments (26).”
From Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [26]
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“As expected, the genotype distribution in the ONTIME population mirrored that in previous genome-wide association study of European ancestry (G allele frequency 5 0.30 with CC, 50%; CG, 40%; and GG, 10%) (26).”
From Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [26]
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Cites
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621
A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. (2007) · Nature · doi:10.1038/nature05616 · Cited by 2,993
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Saxena, R., Voight, B. F., Lyssenko, V., Burtt, N. P., de Bakker, P. I. W., Chen, H., Roix, J. J., Kathiresan, S., Hirschhorn, J. N., Daly, M. J., et al. (2007) · Science · doi:10.1126/science.1142358 · Cited by 2,843
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., et al. (2007) · Science · doi:10.1126/science.1142382 · Cited by 2,753
Self-citationReplication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes
Zeggini, E., Weedon, M. N., Lindgren, C. M., Frayling, T. M., Elliott, K. S., Lango, H., Timpson, N. J., Perry, J. R. B., Rayner, N. W., Freathy, R. M., et al. (2007) · Science · doi:10.1126/science.1142364 · Cited by 2,194
Quantitative estimation of insulin sensitivity.
Bergman, R. N., Ider, Y. Z., Bowden, C. R., & Cobelli, C. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.236.6.e667 · Cited by 1,874
Wellcome Trust Case Control Consortium, Zeggini, E., Scott, L. J., Saxena, R., Voight, B. F., Marchini, J. L., Hu, T., de Bakker, P. I., Abecasis, G. R., Almgren, P., et al. (2008) · Nature Genetics · doi:10.1038/ng.120 · Cited by 1,864
Clinical risk factors, DNA variants, and the development of type 2 diabetes
Lyssenko, V., Jonsson, A., Almgren, P., Pulizzi, N., Isomaa, B., Tuomi, T., Berglund, G., Altshuler, D., Nilsson, P., & Groop, L. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801869 · Cited by 938
Physiological effects of melatonin: Role of melatonin receptors and signal transduction pathways
Pandi-Perumal, S. R., Trakht, I. N., SRINIVASAN, V., SPENCE, D., Maestroni, G. J. M., Zisapel, N., & Cardinali, D. P. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.04.001 · Cited by 799
Variants in MTNR1B influence fasting glucose levels
Prokopenko, I., Langenberg, C., Florez, J. C., Saxena, R., Soranzo, N., Þorleifsson, G., Loos, R. J. F., Manning, A. K., Jackson, A., Aulchenko, Y. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.290 · Cited by 743
Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus
Ward, W. K., Bolgiano, D. C., McKnight, B., Halter, J. B., & Porte, D. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111542 · Cited by 483
Functional and Molecular Defects of Pancreatic Islets in Human Type 2 Diabetes
Del Guerra, S., Lupi, R., Marselli, L., Masini, M., Bugliani, M., Sbrana, S., Torri, S., Pollera, M., Boggi, U., Mosca, F., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.3.727 · Cited by 466
Hanson, R. L., Pratley, R. E., Bogardus, C., Narayan, K. M. V., Roumain, J. M. L., Imperatore, G., Fagot-Campagna, A., Pettitt, D. J., Bennett, P. H., & Knowler, W. C. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010187 · Cited by 463
Family-Based Association Tests for Genomewide Association Scans
Chen, W., & Abecasis, G. R. (2007) · The American Journal of Human Genetics · doi:10.1086/521580 · Cited by 405
Lyssenko, V., Almgren, P., Anevski, D., Perfekt, R., Lahti, K., Nissén, M., Isomaa, B., Forsen, B., Homström, N., Saloranta, C., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.1.166 · Cited by 362
Melatonin, endocrine pancreas and diabetes
Peschke, E. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00519.x · Cited by 309
Evidence for a circadian rhythm of insulin secretion
Boden, G., Ruiz, J., Urbain, J. L., & Chen, X. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.2.e246 · Cited by 261
Patterns of growth among children who later develop type 2 diabetes or its risk factors
Eriksson, J. G., Osmond, C., Kajantie, E., Forsén, T., & Barker, D. J. (2006) · Diabetologia · doi:10.1007/s00125-006-0459-1 · Cited by 257
Long‐term outcome of the Malmö Preventive Project: mortality and cardiovascular morbidity
Berglund, G., Nilsson, P. M., Eriksson, K., Nilsson, J. ‐., Hedblad, B., Kristenson, H., & Lindgärde, F. (2000) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2000.00568.x · Cited by 239
Steil, G., Vølund, A., Kahn, S., & Bergman, R. (1993) · Diabetes · doi:10.2337/diab.42.2.250 · Cited by 234
Modified protocols improve insulin sensitivity estimation using the minimal model
Yang, Y. J., Youn, J. H., & Bergman, R. N. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.6.e595 · Cited by 212
Function and expression of melatonin receptors on human pancreatic islets
Ramracheya, R. D., Muller, D. S., Squires, P. E., Brereton, H., Sugden, D., Huang, G. C., Amiel, S. A., Jones, P. M., & Persaud, S. J. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00523.x · Cited by 186
Melatonin and type 2 diabetes – a possible link?*
Peschke, E., Stumpf, I., Bazwinsky, I., Litvak, L., Dralle, H., & Mühlbauer, E. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00426.x · Cited by 161
Extrapineal Melatonin: Location and Role within Diffuse Neuroendocrine System
Kvetnoy, I. M. (1999) · The Histochemical Journal · doi:10.1023/a:1003431122334 · Cited by 155
Genetic Prediction of Future Type 2 Diabetes
Lyssenko, V., Almgren, P., Anevski, D., Orho‐Melander, M., Sjögren, M., Saloranta, C., Tuomi, T., Groop, L., & the Botnia Study Group (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020345 · Cited by 144
Valle, T. T., Tuomilehto, J., Bergman, R. N., Ghosh, S., Hauser, E. R., Eriksson, J. G., Nylund, S. J., Kohtamäki, K., Toivanen, L., Vidgrén, G., et al. (1998) · Diabetes Care · doi:10.2337/diacare.21.6.949 · Cited by 90
Parallel signaling pathways of melatonin in the pancreatic β‐cell
Peschke, E., Bach, A. G., & Mühlbauer, E. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2005.00297.x · Cited by 82
Marselli, L., Thorne, J., Ahn, Y., Omer, A., Sgroi, D., Libermann, T., Otu, H., Sharma, A. J., Bonner-Weir, S., & Weir, G. (2008) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2007-0931 · Cited by 82
Mühlbauer, E., & Peschke, E. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00399.x · Cited by 74
CART Regulates Islet Hormone Secretion and Is Expressed in the β-Cells of Type 2 Diabetic Rats
Wierup, N., Björkqvist, M., Kuhar, M. J., Mulder, H., & Sundler, F. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db04-1383 · Cited by 65
Endocrine pancreas and diabetes
Hales, C. N. (1980) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(80)90087-0 · Cited by 64
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Transcriptional architecture of the mammalian circadian clock
Takahashi, J. S. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.150 · Cited by 2,786
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
DIAGRAM Consortium, Dupuis, J., GIANT Consortium, Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium, the MAGIC investigators, Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., et al. (2010) · Nature Genetics · doi:10.1038/ng.520 · Cited by 2,166
Metadata
- Authors
- Lyssenko, V., Nagorny, C. L. F., Erdos, M. R., Wierup, N., Jonsson, A., Spégel, P., Bugliani, M., Saxena, R., Fex, M., Pulizzi, N., Isomaa, B., Tuomi, T., Nilsson, P., Kuusisto, J., Tuomilehto, J., Boehnke, M., Altshuler, D., Sundler, F., Eriksson, J. G., Jackson, A. U., Laakso, M., Marchetti, P., Watanabe, R. M., Mulder, H., & Groop, L.
- Affiliations
- Lund University (SE)
- National Human Genome Research Institute (US)
- University of Pisa (IT)
- Broad Institute (US)
- Folkhälsans Forskningscentrum (FI)
- University of Helsinki (FI)
- Kuopio University Hospital (FI)
- University of Michigan (US)
- University of Southern California (US)
- Corresponding author
- Groop, Leif
- ORCID
- Venue
- Nature Genetics
- Published
- 2008-12-07
- Volume
- 41
- Issue
- 1
- Pages
- 82-88
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3725650
- OpenAlex
- W2126776706
- Cited by
- 742
- References
- 31
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 32 · 2023: 28 · 2022: 25 · 2021: 40 · 2020: 33 · 2019: 35 · 2018: 46 · 2017: 50 · 2016: 46 · 2015: 51 · 2014: 48 · 2013: 42 · 2012: 51
- FWCI
- 60.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (Z01HG000024)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072193, U01DK062370, R56DK062370, DK-062370, R01DK062370)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- MTNR1B, type 2 diabetes, insulin secretion, early insulin response, glucose tolerance, pancreatic beta cells, pancreatic islets, melatonin, genetic susceptibility, risk alleles, insulin release inhibition
- MeSH terms
- Insulin Secretion, Aged, Animals, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Protein Transport, Receptors, Melatonin, Receptor, Melatonin, MT2, Mice, Rats
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