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.

Tina Rönn

Tina Rönn

Assistant researcher

Tina Rönn

A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.

Author

  • Thomas Koeck
  • Anders H Olsson
  • Marloes Dekker Nitert
  • Vladimir Sharoyko
  • Claes Ladenvall
  • Olga Kotova
  • Erwin Reiling
  • Tina Rönn
  • Hemang Parikh
  • Jalal Taneera
  • Johan Eriksson
  • Metodi D Metodiev
  • Nils-Göran Larsson
  • Alexander Balhuizen
  • Holger Luthman
  • Alena Stančáková
  • Johanna Kuusisto
  • Markku Laakso
  • Pernille Poulsen
  • Allan Vaag
  • Leif Groop
  • Valeriya Lyssenko
  • Hindrik Mulder
  • Charlotte Ling

Summary, in English

Type 2 diabetes (T2D) evolves when insulin secretion fails. Insulin release from the pancreatic β cell is controlled by mitochondrial metabolism, which translates fluctuations in blood glucose into metabolic coupling signals. We identified a common variant (rs950994) in the human transcription factor B1 mitochondrial (TFB1M) gene associated with reduced insulin secretion, elevated postprandial glucose levels, and future risk of T2D. Because islet TFB1M mRNA levels were lower in carriers of the risk allele and correlated with insulin secretion, we examined mice heterozygous for Tfb1m deficiency. These mice displayed lower expression of TFB1M in islets and impaired mitochondrial function and released less insulin in response to glucose in vivo and in vitro. Reducing TFB1M mRNA and protein in clonal β cells by RNA interference impaired complexes of the mitochondrial oxidative phosphorylation system. Consequently, nutrient-stimulated ATP generation was reduced, leading to perturbed insulin secretion. We conclude that a deficiency in TFB1M and impaired mitochondrial function contribute to the pathogenesis of T2D.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Department of Experimental Medical Science
  • Neuronano Research Center (NRC)
  • Islet cell physiology
  • Genetics
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2011

Language

English

Pages

80-91

Publication/Series

Cell Metabolism

Volume

13

Issue

1

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Neuronano Research Center (NRC)
  • Islet cell physiology
  • Genetics

ISBN/ISSN/Other

  • ISSN: 1550-4131