A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1777934
- author
- 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
; Taneera, Jalal
LU
; Eriksson, Johan
LU
; Metodiev, Metodi D
; Larsson, Nils-Göran
; Balhuizen, Alexander
LU
; Luthman, Holger
LU
; Stančáková, Alena
; Kuusisto, Johanna
; Laakso, Markku
; Poulsen, Pernille
; Vaag, Allan
LU
; Groop, Leif
LU
; Lyssenko, Valeriya
LU
; Mulder, Hindrik
LU
and Ling, Charlotte
LU
(Less) - organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Metabolism
- volume
- 13
- issue
- 1
- pages
- 80 - 91
- publisher
- Cell Press
- external identifiers
-
- wos:000286967400012
- pmid:21195351
- scopus:78650924382
- pmid:21195351
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2010.12.007
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Genetics Unit (013241550), Islet cell physiology (013212142), Neuronano Research Center (NRC) (013210020), Molecular Metabolism (013212001), Department of Clinical Sciences, Malmö (013240000), Diabetes and Endocrinology (013241530)
- 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
- 2016-04-04 08:53:56
- date last changed
- 2024-03-29 19:28:00
@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}},
doi = {{10.1016/j.cmet.2010.12.007}},
volume = {{13}},
year = {{2011}},
}