Pancreatic β cell identity requires continual repression of non–β cell programs

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Pancreatic β cell identity requires continual repression of non-β cell programs.

Loss of β cell identity, the presence of polyhormonal cells, and reprogramming are emerging as important features of β cell dysfunction in patients with type 1 and type 2 diabetes. In this study, we have demonstrated that the transcription factor NKX2.2 is essential for the active maintenance of adult β cell identity as well as function. Deletion of Nkx2.2 in β cells caused rapid onset of a dia...

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Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx.

Adult pancreatic β cells can replicate during growth and after injury to maintain glucose homeostasis. Here, we report that β cells deficient in Dnmt1, an enzyme that propagates DNA methylation patterns during cell division, were converted to α cells. We identified the lineage determination gene aristaless-related homeobox (Arx), as methylated and repressed in β cells, and hypomethylated and ex...

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Fetal PGC-1α Overexpression Programs Adult Pancreatic β-Cell Dysfunction

Adult β-cell dysfunction, a hallmark of type 2 diabetes, can be programmed by adverse fetal environment. We have shown that fetal glucocorticoids (GCs) participate in this programming through inhibition of β-cell development. Here we have investigated the molecular mechanisms underlying this regulation. We showed that GCs stimulate the expression of peroxisome proliferator-activated receptor-γ ...

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Impact of Magnesium Deficiency on Pancreatic β-Cell Function in Type 2 Diabetic Nigerians

Objective: Pancreatic b-cell dysfunction is described to be present at the diagnosis of type 2 diabetes mellitus (T2DM) and progressively deteriorated with disease duration. However, its progression is variable and potentially influenced by several factors. The Magnesium (Mg) deficiency mediates insulin resistance but reports regarding its role in pancreatic β-cell dysfunction are scarce and co...

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Pancreatic beta cell identity is maintained by DNA methylation- mediated repression of Arx

Adult pancreatic beta cells can replicate during growth and after injury to maintain glucose homeostasis. Here we report that beta cells deficient in Dnmt1, an enzyme that propagates DNA methylation patterns during cell division, were converted to alpha cells. We identified the lineage determination gene aristaless related homeobox (Arx), as methylated and repressed in beta cells, and hypo-meth...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2016

ISSN: 0021-9738,1558-8238

DOI: 10.1172/jci88017