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BMC Medical Genomics

, 4:86

Functional and structural genomics

Abstract

BackgroundThe progression towards type 2 diabetes depends on the allostatic response of 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 physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob-ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob-ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion

ResultsHere we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob-ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob-ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance-activation of mechanisms essential for the continued function of the beta cell.

ConclusionsOur data suggest that the expansion of beta cell mass observed in ob-ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-4-86 contains supplementary material, which is available to authorized users.

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Autor: Yurena Vivas - Cristina Martínez-García - Adriana Izquierdo - Francisco Garcia-Garcia - Sergio Callejas - Ismael Velasco -

Fuente: https://link.springer.com/







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