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

Koeck, Thomas; Olsson, Anders H LU ; Dekker Nitert, Marloes LU ; Sharoyko, Vladimir LU ; Ladenvall, Claes LU ; Kotova, Olga LU ; Reiling, Erwin LU ; Rönn, Tina LU ; Parikh, Hemang and Taneera, Jalal LU , et al. (2011) In Cell Metabolism 13(1). p.80-91
Abstract
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... (More)
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. (Less)
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Contribution to journal
publication status
published
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Cell Metabolism
volume
13
issue
1
pages
80 - 91
publisher
Cell Press
external identifiers
  • wos:000286967400012
  • pmid:21195351
  • scopus:78650924382
ISSN
1550-4131
DOI
10.1016/j.cmet.2010.12.007
language
English
LU publication?
yes
id
1ae5114e-e0d0-485d-acd0-4c188c8cec19 (old id 1777934)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21195351?dopt=Abstract
date added to LUP
2011-02-01 10:22:57
date last changed
2017-09-24 04:39:41
@article{1ae5114e-e0d0-485d-acd0-4c188c8cec19,
  abstract     = {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.},
  author       = {Koeck, Thomas and Olsson, Anders H and Dekker Nitert, Marloes and Sharoyko, Vladimir and Ladenvall, Claes and Kotova, Olga and Reiling, Erwin and Rönn, Tina and Parikh, Hemang and Taneera, Jalal and Eriksson, Johan and Metodiev, Metodi D and Larsson, Nils-Göran and Balhuizen, Alexander and Luthman, Holger and Stančáková, Alena and Kuusisto, Johanna and Laakso, Markku and Poulsen, Pernille and Vaag, Allan and Groop, Leif and Lyssenko, Valeriya and Mulder, Hindrik and Ling, Charlotte},
  issn         = {1550-4131},
  language     = {eng},
  number       = {1},
  pages        = {80--91},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2010.12.007},
  volume       = {13},
  year         = {2011},
}