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

Koeck, Thomas, Olsson, Anders H., Nitert, Marloes Dekker, Sharoyko, Vladimir V., Ladenvall, Claes, Kotova, Olga, Reiling, Erwin, Ronn, Tina, Parikh, Hemang, Taneera, Jalal, Eriksson, Johan G., Metodiev, Metodi D., Larsson, Nils-Goran, Balhuizen, Alexander, Luthman, Holger, Stancakova, Alena, Kuusisto, Johanna, Laakso, Markku, Poulsen, Pernille, Vaag, Allan, Groop, Leif, Lyssenko, Valeriya, Mulder, Hindrik and Ling, Charlotte (2011) A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes. Cell Metabolism, 13 1: 80-91.


Author Koeck, Thomas
Olsson, Anders H.
Nitert, Marloes Dekker
Sharoyko, Vladimir V.
Ladenvall, Claes
Kotova, Olga
Reiling, Erwin
Ronn, Tina
Parikh, Hemang
Taneera, Jalal
Eriksson, Johan G.
Metodiev, Metodi D.
Larsson, Nils-Goran
Balhuizen, Alexander
Luthman, Holger
Stancakova, Alena
Kuusisto, Johanna
Laakso, Markku
Poulsen, Pernille
Vaag, Allan
Groop, Leif
Lyssenko, Valeriya
Mulder, Hindrik
Ling, Charlotte
Title A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes
Journal name Cell Metabolism  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2011-01
Sub-type Article
DOI 10.1016/j.cmet.2010.12.007
Volume number 13
Issue number 1
ISSN 1550-4131
Start page 80
End page 91
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Collection year 2012
Language eng
Formatted 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.
Keyword Human Skeletal-Muscle
Mitochondrial Dysfunction
Gene-Expression
Complex-I
Dna
Mutation
Transcription
Methylation
Deficiency
Metabolism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article
Collections: Non HERDC
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 34 Abstract Views  -  Detailed Statistics
Created: Tue, 20 Sep 2011, 13:55:23 EST by System User on behalf of School of Medicine