RGD Reference Report - Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. - Rat Genome Database

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Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.

Authors: Lyssenko, V  Nagorny, CL  Erdos, MR  Wierup, N  Jonsson, A  Spegel, 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, JG  Jackson, AU  Laakso, M  Marchetti, P  Watanabe, RM  Mulder, H  Groop, L 
Citation: Lyssenko V, etal., Nat Genet. 2009 Jan;41(1):82-8. doi: 10.1038/ng.288. Epub 2008 Dec 7.
RGD ID: 9588652
Pubmed: PMID:19060908   (View Abstract at PubMed)
PMCID: PMC3725650   (View Article at PubMed Central)
DOI: DOI:10.1038/ng.288   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IEP 9588652 RGD 
type 2 diabetes mellitus  ISOMTNR1B (Homo sapiens)9588652; 9588652 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtnr1b  (melatonin receptor 1B)

Genes (Mus musculus)
Mtnr1b  (melatonin receptor 1B)

Genes (Homo sapiens)
MTNR1B  (melatonin receptor 1B)


Additional Information