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Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

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...

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Autores principales: Salas, Elisabet, Rabhi, Nabil, Froguel, Philippe, Annicotte, Jean-Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941170/
https://www.ncbi.nlm.nih.gov/pubmed/24672805
http://dx.doi.org/10.1155/2014/873679
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author Salas, Elisabet
Rabhi, Nabil
Froguel, Philippe
Annicotte, Jean-Sébastien
author_facet Salas, Elisabet
Rabhi, Nabil
Froguel, Philippe
Annicotte, Jean-Sébastien
author_sort Salas, Elisabet
collection PubMed
description 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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spelling pubmed-39411702014-03-26 Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions Salas, Elisabet Rabhi, Nabil Froguel, Philippe Annicotte, Jean-Sébastien J Diabetes Res Review Article 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. Hindawi Publishing Corporation 2014 2014-02-06 /pmc/articles/PMC3941170/ /pubmed/24672805 http://dx.doi.org/10.1155/2014/873679 Text en Copyright © 2014 Elisabet Salas et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Salas, Elisabet
Rabhi, Nabil
Froguel, Philippe
Annicotte, Jean-Sébastien
Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title_full Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title_fullStr Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title_full_unstemmed Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title_short Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
title_sort role of ink4a/arf locus in beta cell mass expansion under physiological and pathological conditions
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941170/
https://www.ncbi.nlm.nih.gov/pubmed/24672805
http://dx.doi.org/10.1155/2014/873679
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