دورية أكاديمية
Pancreatic alpha-cell mass in the early-onset and advanced stage of a mouse model of experimental autoimmune diabetes
| العنوان: | Pancreatic alpha-cell mass in the early-onset and advanced stage of a mouse model of experimental autoimmune diabetes |
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| المؤلفون: | Bru-Tarí, Eva, Cobo-Vuilleumier, Nadia, Alonso-Magdalena, Paloma, Dos Santos, Reinaldo S., Marroqui, Laura, Nadal, Ángel, Gauthier, Benoit R., Quesada, Iván |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | Most studies in type 1 diabetes (T1D) have focused on the loss of the pancreatic beta-cell population. However, despite the involvement of the alpha-cell in the aetiology and complications of T1D, little is known about the regulation of the pancreatic alpha-cell mass in this disease. The need for a better understanding of this process is further emphasized by recent findings suggesting that alpha-cells may constitute a potential reservoir for beta-cell regeneration. In this study, we characterized the pancreatic alpha-cell mass and its regulatory processes in the transgenic RIP-B7.1 mice model of experimental autoimmune diabetes (EAD). Diabetic mice presented insulitis, hyperglycaemia, hypoinsulinemia and hyperglucagonemia along with lower pancreatic insulin content. While alpha-cell mass and pancreatic glucagon content were preserved at the early-onset of EAD, both parameters were reduced in the advanced phase. At both stages, alpha-cell size, proliferation and ductal neogenesis were up-regulated, whereas apoptosis was almost negligible. Interestingly, we found an increase in the proportion of glucagon-containing cells positive for insulin or the beta-cell transcription factor PDX1. Our findings suggest that pancreatic alpha-cell renewal mechanisms are boosted during the natural course of EAD, possibly as an attempt to maintain the alpha-cell population and/or to increase beta-cell regeneration via alpha-cell transdifferentiation. ; This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (BFU2013-42789; BFU2017-86579-R; BFU2016-77125-R; BFU2017-83588-P), Generalitat Valenciana (PROMETEOII/2015/016) and the Juvenile Diabetes Research Foundation (17-2013-372 to B.R.G.). L.M. holds a Juan de la Cierva fellowship from the Ministerio de Ciencia, Innovación y Universidades (IJCI-2015-24482). CIBERDEM is an initiative of the Instituto de Salud Carlos III. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-42789-P; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-86579-R; BFU2017-86579-R/AEI/10.13039/501100011033; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-77125-R; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-83588-P; BFU2017-83588-P/AEI/10.13039/501100011033; Publisher's version; http://dx.doi.org/10.1038/s41598-019-45853-1Test; Sí; e-issn: 2045-2322; Scientific Reports 9: 9515 (2019); http://hdl.handle.net/10261/202643Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100000780Test |
| DOI: | 10.1038/s41598-019-45853-1 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100000780 |
| الإتاحة: | https://doi.org/10.1038/s41598-019-45853-1Test https://doi.org/10.13039/501100011033Test https://doi.org/10.13039/501100000780Test http://hdl.handle.net/10261/202643Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.CD513D52 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-019-45853-1 |
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