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A common variant in...
A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
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Koeck, Thomas (author)
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- Olsson, Anders H (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Dekker Nitert, Marloes (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Sharoyko, Vladimir (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Ladenvall, Claes (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Kotova, Olga (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Reiling, Erwin (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Rönn, Tina (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Parikh, Hemang (author)
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- Taneera, Jalal (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Eriksson, Johan (author)
- Lund University,Lunds universitet,Neuronano Research Center (NRC),Forskargrupper vid Lunds universitet,Lund University Research Groups
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Metodiev, Metodi D (author)
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- Larsson, Nils-Göran (author)
- Karolinska Institutet
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- Balhuizen, Alexander (author)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Luthman, Holger (author)
- Lund University,Lunds universitet,Genetik,Forskargrupper vid Lunds universitet,Genetics,Lund University Research Groups
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Stančáková, Alena (author)
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Kuusisto, Johanna (author)
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Laakso, Markku (author)
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Poulsen, Pernille (author)
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- Vaag, Allan (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Lyssenko, Valeriya (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- English.
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 13:1, s. 80-91
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Koeck, Thomas
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Olsson, Anders H
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Dekker Nitert, M ...
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Sharoyko, Vladim ...
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Ladenvall, Claes
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Kotova, Olga
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show more...
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Reiling, Erwin
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Rönn, Tina
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Parikh, Hemang
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Taneera, Jalal
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Eriksson, Johan
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Metodiev, Metodi ...
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Larsson, Nils-Gö ...
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Balhuizen, Alexa ...
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Luthman, Holger
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Stančáková, Alen ...
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Kuusisto, Johann ...
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Laakso, Markku
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Poulsen, Pernill ...
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Vaag, Allan
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Groop, Leif
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Lyssenko, Valeri ...
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Mulder, Hindrik
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Ling, Charlotte
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell Metabolism
- By the university
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Lund University
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Karolinska Institutet