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Träfflista för sökning "WFRF:(Akerman Ildem) "

Sökning: WFRF:(Akerman Ildem)

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1.
  • Akerman, Ildem, et al. (författare)
  • Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
  • 2017
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 25:2, s. 400-411
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
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2.
  • Allen, Hana Lango, et al. (författare)
  • GATA6 haploinsufficiency causes pancreatic agenesis in humans.
  • 2012
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:1, s. 20-2
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the regulation of pancreatic development is key for efforts to develop new regenerative therapeutic approaches for diabetes. Rare mutations in PDX1 and PTF1A can cause pancreatic agenesis, however, most instances of this disorder are of unknown origin. We report de novo heterozygous inactivating mutations in GATA6 in 15/27 (56%) individuals with pancreatic agenesis. These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development.
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3.
  • Tattikota, Sudhir G, et al. (författare)
  • Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell.
  • 2014
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 19:1, s. 122-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.
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  • Resultat 1-3 av 3

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