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首页> 外文期刊>BMC Medical Genomics >Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass
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Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

机译：早期过氧化物酶体增殖物激活的受体γ调控的基因参与胰腺β细胞团的扩增

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Background The 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 Results Here 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. Conclusions Our 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.
机译：背景技术2型糖尿病的进展取决于胰腺β细胞对合成和分泌足够的胰岛素以补偿胰岛素抵抗的同种异体反应。内分泌胰腺是一种可塑性组织，能够响应与胰岛素抵抗相关的生理和病理生理状态（例如怀孕，肥胖或衰老）所施加的要求而扩张或退缩，但在这些情况下介​​导β细胞质量扩张的机制尚不清楚。我们最近发现，具有PPARγ2遗传切除功能的ob / ob小鼠（一种称为POKO小鼠的小鼠模型）未能扩大其β细胞质量。这种表型与在其肥胖同窝ob / ob小鼠中观察到的β细胞质量的适当扩展形成对照。因此，比较这些模型胰岛，尤其是在早期，可以为参与β细胞大规模扩增过程的早期PPARγ依赖性转录反应提供一些新见识。结果在这里，我们研究了在β细胞适应于早期阶段的PPARγ依赖性转录反应。野生型，ob / ob，PPARγ2KO和POKO小鼠的胰岛素抵抗。我们已经确定了已知可调节β细胞增殖速率和存活信号的基因。此外，我们还发现了在ob / ob胰岛中诱导的新途径，在POKO胰岛中保持不变，这表明PPARγ在维持/激活β细胞持续功能所必需的机制中具有重要作用。结论我们的数据表明，在ob / ob胰岛中观察到的β细胞团块扩张与免疫应答的激活有关，而在POKO胰岛中未发生这种免疫应答。我们还确定了其他PPARγ依赖的差异调节途径，包括胆固醇生物合成，通过TGF-β信号传导引起的细胞凋亡和氧化磷酸化的降低。

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