Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.
(2009) In Nature Genetics 41(1). p.82-88- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1276379
- author
- Lyssenko, Valeriya
; Nagorny, Cecilia
LU
; Erdos, Michael R
; Wierup, Nils
LU
; Jonsson, Anna
LU
; Spégel, Peter
LU
; Bugliani, Marco
; Saxena, Richa
; Fex, Malin
LU
; Pulizzi, Nicolo
LU
; Isomaa, Bo
; Tuomi, Tiinamaija
LU
; Nilsson, Peter
LU
; Kuusisto, Johanna
; Tuomilehto, Jaakko
; Boehnke, Michael
; Altshuler, David
; Sundler, Frank
LU
; Eriksson, Johan G
; Jackson, Anne U
; Laakso, Markku
; Marchetti, Piero
; Watanabe, Richard M
; Mulder, Hindrik
LU
and Groop, Leif
LU
(Less) - organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Genetics
- volume
- 41
- issue
- 1
- pages
- 82 - 88
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000262085300020
- pmid:19060908
- scopus:58149175669
- pmid:19060908
- ISSN
- 1546-1718
- DOI
- 10.1038/ng.288
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Diabetes and Endocrinology (013241530), Internal Medicine Research Unit (013242520), Diabetes and Celiac Unit (013241540), Endocrinology (013241500), Neuroendocrine Cell Biology (013212008), Molecular Metabolism (013212001)
- id
- 14eac4a4-1876-400b-b454-15977c5178d3 (old id 1276379)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19060908?dopt=Abstract
- date added to LUP
- 2016-04-04 09:36:59
- date last changed
- 2024-03-30 05:58:02
@article{14eac4a4-1876-400b-b454-15977c5178d3,
abstract = {{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.}},
author = {{Lyssenko, Valeriya and Nagorny, Cecilia and Erdos, Michael R and Wierup, Nils and Jonsson, Anna and Spégel, Peter and Bugliani, Marco and Saxena, Richa and Fex, Malin and Pulizzi, Nicolo and Isomaa, Bo and Tuomi, Tiinamaija and Nilsson, Peter and Kuusisto, Johanna and Tuomilehto, Jaakko and Boehnke, Michael and Altshuler, David and Sundler, Frank and Eriksson, Johan G and Jackson, Anne U and Laakso, Markku and Marchetti, Piero and Watanabe, Richard M and Mulder, Hindrik and Groop, Leif}},
issn = {{1546-1718}},
language = {{eng}},
number = {{1}},
pages = {{82--88}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.}},
url = {{http://dx.doi.org/10.1038/ng.288}},
doi = {{10.1038/ng.288}},
volume = {{41}},
year = {{2009}},
}