Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

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

Author

  • Valeriya Lyssenko
  • Cecilia Nagorny
  • Michael R Erdos
  • Nils Wierup
  • Anna Jonsson
  • Peter Spégel
  • Marco Bugliani
  • Richa Saxena
  • Malin Fex
  • Nicolo Pulizzi
  • Bo Isomaa
  • Tiinamaija Tuomi
  • Peter Nilsson
  • Johanna Kuusisto
  • Jaakko Tuomilehto
  • Michael Boehnke
  • David Altshuler
  • Frank Sundler
  • Johan G Eriksson
  • Anne U Jackson
  • Markku Laakso
  • Piero Marchetti
  • Richard M Watanabe
  • Hindrik Mulder
  • Leif Groop

Summary, in English

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.

Department/s

  • Department of Experimental Medical Science
  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • Internal Medicine - Epidemiology

Publishing year

2009

Language

English

Pages

82-88

Publication/Series

Nature Genetics

Volume

41

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1546-1718