Key result
This review summarizes the role of the ARF/INK4A (Cdkn2a) locus in beta cell cycle regulation, senescence, and diabetes development, highlighting regeneration strategies like long noncoding RNAs.
This review highlights the critical role of the Cdkn2a locus in beta cell senescence and potential therapeutic targets for beta cell regeneration in diabetes.
Cdkn2a locus supports mechanistic insights into beta-cell senescence; leaves open lncRNA regeneration strategies for clinical translation in diabetes.
The ARF/INK4A (Cdkn2a) locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice) that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin.
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Salas et al. (2014) conducted a review in Diabetes and beta cell senescence. This review summarizes the role of the ARF/INK4A (Cdkn2a) locus in beta cell cycle regulation, senescence, and diabetes development, highlighting regeneration strategies like long noncoding RNAs.
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