A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
80-91
Publikation/Tidskrift/Serie
Cell Metabolism
Volym
13
Issue
1
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Genomics, Diabetes and Endocrinology
- Neuronano Research Center (NRC)
- Islet cell physiology
- Genetics
ISBN/ISSN/Övrigt
- ISSN: 1550-4131