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Common variant in M...
Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.
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Lyssenko, Valeriya (author)
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- Nagorny, Cecilia (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Erdos, Michael R (author)
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- Wierup, Nils (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Jonsson, Anna (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Spégel, Peter (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Bugliani, Marco (author)
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Saxena, Richa (author)
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- Fex, Malin (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups
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- Pulizzi, Nicolo (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Isomaa, Bo (author)
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- Tuomi, Tiinamaija (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Nilsson, Peter (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
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Kuusisto, Johanna (author)
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Tuomilehto, Jaakko (author)
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Boehnke, Michael (author)
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Altshuler, David (author)
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- Sundler, Frank (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Eriksson, Johan G (author)
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Jackson, Anne U (author)
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Laakso, Markku (author)
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Marchetti, Piero (author)
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Watanabe, Richard M (author)
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- 2008-12-07
- 2009
- English.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 82-88
- Related links:
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http://dx.doi.org/10...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lyssenko, Valeri ...
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Nagorny, Cecilia
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Erdos, Michael R
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Wierup, Nils
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Jonsson, Anna
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Spégel, Peter
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show more...
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Bugliani, Marco
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Saxena, Richa
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Fex, Malin
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Pulizzi, Nicolo
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Isomaa, Bo
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Tuomi, Tiinamaij ...
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Nilsson, Peter
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Kuusisto, Johann ...
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Tuomilehto, Jaak ...
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Boehnke, Michael
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Altshuler, David
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Sundler, Frank
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Eriksson, Johan ...
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Jackson, Anne U
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Laakso, Markku
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Marchetti, Piero
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Watanabe, Richar ...
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Mulder, Hindrik
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Groop, Leif
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Genetics
- By the university
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Lund University