Regulation of ER Homeostasis and Cell Cycle by Pax4 Enhances β-Cell Survival and Protects Mice Against Experimental Autoimmune Diabetes

ABSTRACT: Strategies to enhance islet b-cell survival and regeneration while refraining inflammation through manipulation of molecular targets would provide means to stably replenish the deteriorating functional b-cell mass detected in both Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM). Herein we report that over expression of the islet enriched transcription factor Pax4 refrains development of hyperglycemia in the RIP-B7.1 mouse model of T1DM through reduced insulitis, decreased b-cell apoptosis correlating with diminished DNA damage and increased proliferation. Transcriptomics revealed up regulation of genes involved in immunomodulation, cell cycle and ER homeostasis in islets over expressing Pax4 as compared to the T2DM-linked mutant variant Pax4R129W. Pax4 but not Pax4R129W protected islet

ORGANISM(S): Mus musculus

SUBMITTER: Benoit Gauthier 

PROVIDER: E-GEOD-62846 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress