| dc.contributor.advisor | Mansouri, Ahmed Prof. Dr. | |
| dc.contributor.author | Shamsi, Farnaz | |
| dc.date.accessioned | 2014-09-30T08:17:37Z | |
| dc.date.available | 2014-09-30T08:17:37Z | |
| dc.date.issued | 2014-09-30 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-98E8-9 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4696 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Pancreatic β-Cell Regeneration in TIF-IA Knockout Mice | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Pieler, Tomas Prof. Dr. | |
| dc.date.examination | 2014-07-02 | |
| dc.description.abstracteng | As the sole source of insulin production in body, pancreatic β-cells play an essential role in glucose homeostasis. Diabetes mellitus is a chronic disease characterized by loss, reduction, and/or malfunction of β-cell mass. The putative induction of adult β-cell regeneration repre- sents a promising approach for the treatment of type 1 diabetes. Towards this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel β-cell ablation mouse model, in which the β-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the β-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA∆/∆). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted β-cell death. In this model, we observed β-cell regenera- tion that resulted in a complete recovery of the β-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining β-cells is the prominent mechanism acting to compensate for the massive β-cell loss in young but also aged mice. Interestingly, at any age, we also detected β-like cells expressing the glucagon hormone, suggesting a transition between α and β-cell identities or vice versa. Taken together, the (TIF-IA∆/∆) mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting β-cell regeneration. RNA-sequencing of (TIF-IA∆/∆) pancreas provided the possibilty to look at β-cell regeneration at the molecular level and dissect out the cellular pathways induced in pancreas upon β-cell ablation. These signaling pathways work together to mediate β-cell stress response, metabolic adaptations, and tissue homeostasis. Using these data, we have identified some novel regulators of β-cell regeneration. | de |
| dc.contributor.coReferee | Schuh, Reinhard Prof. Dr. | |
| dc.contributor.thirdReferee | Stoykova, Anastassia Prof. Dr. | |
| dc.contributor.thirdReferee | Wimmer, Ernst A. Prof. Dr. | |
| dc.contributor.thirdReferee | Dosch, Roland Dr. | |
| dc.subject.eng | Pancreas | de |
| dc.subject.eng | Beta-cell regeneration | de |
| dc.subject.eng | Diabetes | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-98E8-9-4 | |
| dc.affiliation.institute | Biologische Fakultät für Biologie und Psychologie | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 797782575 | |