Argonaute2 mediates compensatory expansion of the pancreatic ß-cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46623 | GEO | 2014/02/06
SECONDARY ACCESSION(S): PRJNA201244
REPOSITORIES: GEO
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Project description:The progression towards type 2 diabetes depends on the success of the allostatic response of the pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physio and pathological states such as pregnancy, obesity or ageing. The mechanisms, mediating beta cell mass expansion in these scenarios are not well defined. We have recently showed that beta cell mass failed to expand in ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Here we investigate PPAR gamma dependent transcriptional responses occurring during early stages of the adaptation of beta cells to insulin resistance. As it could be expected we have identified genes known to regulate proliferation and survival signals of the beta cells. Moreover we have also identified new pathways induced in ob/ob islets that fail to do so in POKO islets. Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with activation of immune response and is missing in POKO islets. Other PPARγ dependent differentially regulated pathways include cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.
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