TY - JOUR UR - http://lib.ugent.be/catalog/pug01:8043210 ID - pug01:8043210 LA - eng TI - Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes PY - 2016 JO - (2016) NATURE GENETICS SN - 1061-4036 PB - 2016 AU - Dooley, James AU - Tian, Lei AU - Schonefeldt, Susann AU - Delghingaro-Augusto, Viviane AU - Garcia-Perez, Josselyn E AU - Pasciuto, Emanuela AU - Di Marino, Daniele AU - Carr, Edward J AU - Oskolkov, Nikolay AU - Lyssenko, Valeriya AU - Franckaert, Dean AU - Lagou, Vasiliki AU - Overbergh, Lut AU - Vandenbussche, Jonathan UGent 802000883544 AU - Allemeersch, Joke AU - Chabot-Roy, Genevieve AU - Dahlstrom, Jane E AU - Laybutt, D Ross AU - Petrovsky, Nikolai AU - Socha, Luis AU - Gevaert, Kris GE31 801001024116 0000-0002-4237-0283 AU - Jetten, Anton M AU - Lambrechts, Diether AU - Linterman, Michelle A AU - Goodnow, Chris C AU - Nolan, Christopher J AU - Lesage, Sylvie AU - Schlenner, Susan M AU - Liston, Adrian AB - 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.Keywords ER -Download RIS file
00000nam^a2200301^i^4500 | |||
001 | 8043210 | ||
005 | 20161219153924.0 | ||
008 | 160802s2016------------------------eng-- | ||
022 | a 1061-4036 | ||
024 | a 000374834100011 2 wos | ||
024 | a 1854/LU-8043210 2 handle | ||
024 | a 10.1038/ng.3531 2 doi | ||
040 | a UGent | ||
245 | a Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes | ||
260 | c 2016 | ||
520 | a 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.Keywords | ||
598 | a A1 | ||
700 | a Dooley, James | ||
700 | a Tian, Lei | ||
700 | a Schonefeldt, Susann | ||
700 | a Delghingaro-Augusto, Viviane | ||
700 | a Garcia-Perez, Josselyn E | ||
700 | a Pasciuto, Emanuela | ||
700 | a Di Marino, Daniele | ||
700 | a Carr, Edward J | ||
700 | a Oskolkov, Nikolay | ||
700 | a Lyssenko, Valeriya | ||
700 | a Franckaert, Dean | ||
700 | a Lagou, Vasiliki | ||
700 | a Overbergh, Lut | ||
700 | a Vandenbussche, Jonathan u UGent 0 802000883544 0 976875908654 9 2EF44520-F0EE-11E1-A9DE-61C894A0A6B4 | ||
700 | a Allemeersch, Joke | ||
700 | a Chabot-Roy, Genevieve | ||
700 | a Dahlstrom, Jane E | ||
700 | a Laybutt, D Ross | ||
700 | a Petrovsky, Nikolai | ||
700 | a Socha, Luis | ||
700 | a Gevaert, Kris u GE31 0 801001024116 0 0000-0002-4237-0283 9 F4EC703C-F0ED-11E1-A9DE-61C894A0A6B4 | ||
700 | a Jetten, Anton M | ||
700 | a Lambrechts, Diether | ||
700 | a Linterman, Michelle A | ||
700 | a Goodnow, Chris C | ||
700 | a Nolan, Christopher J | ||
700 | a Lesage, Sylvie | ||
700 | a Schlenner, Susan M | ||
700 | a Liston, Adrian | ||
650 | a Chemistry | ||
653 | a MOLECULAR-DYNAMICS | ||
653 | a NOD MOUSE | ||
653 | a UNFOLDED PROTEIN RESPONSE | ||
653 | a HUMAN PANCREATIC-ISLETS | ||
653 | a TRANSGENIC MOUSE MODEL | ||
653 | a RNA-SEQ | ||
653 | a MICE | ||
653 | a KeyWords Plus:ENDOPLASMIC-RETICULUM STRESS | ||
653 | a DNA-SEQUENCING DATA | ||
653 | a T-CELLS | ||
773 | t NATURE GENETICS g Nature Genet. 2016. 48 (5) p.519-527 q 48:5<519 | ||
856 | 3 Full Text u https://biblio.ugent.be/publication/8043210/file/8043626 z [ugent] y 2016_Dooley_NatGenetics.pdf | ||
920 | a article | ||
Z30 | x VI 1 VIB | ||
922 | a UGENT-EA | ||
Z30 | x GE 1 GE07 | ||
922 | a UGENT-GE |
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