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. doi:10.1016/j.cmet.2010.12.007

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   Check publisher's open access policy
ISSN 1550-4131
Publication date 2011-01
Sub-type Article (original research)
DOI 10.1016/j.cmet.2010.12.007
Volume 13
Issue 1
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
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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