Nature genetics, 2009-01, Vol.41 (1), p.82-88
- LYSSENKO, Valeriya
- NAGORNY, Cecilia L. F
- ISOMAA, Bo
- TUOMI, Tiinamaija
- NILSSON, Peter
- KUUSISTO, Johanna
- TUOMILEHTO, Jaakko
- BOEHNKE, Michael
- ALTSHULER, David
- SUNDLER, Frank
- ERIKSSON, Johan G
- JACKSON, Anne U
- ERDOS, Michael R
- LAAKSO, Markku
- MARCHETTI, Piero
- WATANABE, Richard M
- MULDER, Hindrik
- GROOP, Leif
- WIERUP, Nils
- JONSSON, Anna
- SPEGEL, Peter
- BUGLIANI, Marco
- SAXENA, Richa
- FEX, Malin
- PULIZZI, Nicolo
2009
Details
- Autor(en) / Beteiligte
- LYSSENKO, Valeriya
- NAGORNY, Cecilia L. F
- ISOMAA, Bo
- TUOMI, Tiinamaija
- NILSSON, Peter
- KUUSISTO, Johanna
- TUOMILEHTO, Jaakko
- BOEHNKE, Michael
- ALTSHULER, David
- SUNDLER, Frank
- ERIKSSON, Johan G
- JACKSON, Anne U
- ERDOS, Michael R
- LAAKSO, Markku
- MARCHETTI, Piero
- WATANABE, Richard M
- MULDER, Hindrik
- GROOP, Leif
- WIERUP, Nils
- JONSSON, Anna
- SPEGEL, Peter
- BUGLIANI, Marco
- SAXENA, Richa
- FEX, Malin
- PULIZZI, Nicolo
- Titel
- Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion
- Ist Teil von
- Nature genetics, 2009-01, Vol.41 (1), p.82-88
- Ort / Verlag
- New York, NY: Nature Publishing Group
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1061-4036, 1546-1718eISSN: 1546-1718DOI: 10.1038/ng.288Titel-ID: cdi_swepub_primary_oai_lup_lub_lu_se_14eac4a4_1876_400b_b454_15977c5178d3
- Format
- –
- Schlagworte
- Aged, Animals, Biological and medical sciences, Cell physiology, Clinical Medicine, Cohort Studies, Data analysis, Diabetes, Diabetes Mellitus, Type 2 - genetics, Diabetes. Impaired glucose tolerance, Endocrine pancreas. Apud cells (diseases), Endocrinology and Diabetes, Endocrinopathies, Endokrinologi och diabetes, Etiopathogenesis. Screening. Investigations. Target tissue resistance, Female, Fundamental and applied biological sciences. Psychology, Gene Expression Regulation, Genes, Genetic Predisposition to Disease, Genetics, Genetics of eukaryotes. Biological and molecular evolution, Humans, Insulin, Insulin - metabolism, Insulin Secretion, Islets of Langerhans - metabolism, Islets of Langerhans - pathology, Klinisk medicin, Male, Medical and Health Sciences, Medical sciences, Medicin och hälsovetenskap, Melatonin, Metabolic syndrome, Mice, Middle Aged, Molecular and cellular biology, Polymorphism, Single Nucleotide - genetics, Protein Transport, Rats, Receptor, Melatonin, MT2 - genetics, Receptor, Melatonin, MT2 - metabolism, Receptors, Melatonin - genetics, Receptors, Melatonin - metabolism, Risk factors, Secretion. Exocytosis, Studies