Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

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Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

Dooley, James (author): Catholic University of Leuven

Tian, Lei (author): Catholic University of Leuven

Schonefeldt, Susann (author): Catholic University of Leuven

Delghingaro-Augusto, Viviane (author): Australian National University

Garcia-Perez, Josselyn E (author): Catholic University of Leuven

Pasciuto, Emanuela (author): Catholic University of Leuven

Di Marino, Daniele (author): Università della Svizzera Italiana

Carr, Edward J (author): Babraham Institute

Oskolkov, Nikolay (author): Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups

Lyssenko, Valeriya (author): Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups

Franckaert, Dean (author): Catholic University of Leuven

Lagou, Vasiliki (author)

Overbergh, Lut (author)

Vandenbussche, Jonathan (author)

Allemeersch, Joke (author)

Chabot-Roy, Genevieve (author)

Dahlstrom, Jane E (author)

Laybutt, D Ross (author)

Petrovsky, Nikolai (author)

Socha, Luis (author)

Gevaert, Kris (author)

Jetten, Anton M (author)

Lambrechts, Diether (author)

Linterman, Michelle A (author)

Goodnow, Chris C (author)

Nolan, Christopher J (author)

Lesage, Sylvie (author)

Schlenner, Susan M (author)

Liston, Adrian (author)

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(creator_code:org_t)

2016-03-21
2016
English.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 519-527

Related links:: http://dx.doi.org/10...; show more...; https://europepmc.or...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes.

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: Nature Genetics

By the university: Lund University

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Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

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