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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
Publishing year: 2011
Language: English
Pages: 80-91
Publication/Series: Cell Metabolism
Volume: 13
Issue: 1
Document type: Journal article
Publisher: Cell Press

Abstract 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.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Diabetes and Endocrinology
  • Neuronano Research Center (NRC)
  • Islet cell physiology
  • Medical Genetics Unit
  • ISSN: 1550-4131
Tina Rönn
E-mail: tina [dot] ronn [at] med [dot] lu [dot] se

Assistant researcher

Epigenetics and Diabetes

+46 40 39 12 18

CRC 91-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00