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Expression profiles of stress-related genes in islets from donors with progressively impaired glucose metabolism

机译:含有逐渐受损的葡萄糖代谢含量含量的含量应力相关基因的表达谱

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ABSTRACT: It is currently unknown how the islet transcriptional pattern changes as glucose metabolism deteriorates and progresses to fulminant type 2 diabetes (T2D). In this study, we hypothesized that islets from donors with elevated HbA1c levels, but not yet diagnosed with T2D, would show signs of cell stress on a transcriptional level. Laser capture microdissection and qPCR arrays including 330 genes related to mitochondria, oxidative stress, or the unfolded protein response were used to extract and analyze islets from organ donors with HbA1c <5.5% (37 mmol/mol), elevated HbA1c (6.0–6.5% (42–48 mmol/mol)), high HbA1c (>6.5% (48 mmol/mol)) or established T2D. Principal component analysis and hierarchical clustering based on the expression of all 330 genes displayed no obvious separation of the four different donor groups, indicating that the inter-donor variations were larger than the differences between groups. However, 44 genes were differentially expressed (P < 0.05, false discovery rate <30%) between islets from donors with HbA1c <5.5% (37 mmol/mol) compared with islets from T2D subjects. Twelve genes were differentially expressed compared to control islets in both donors with established T2D and donors with elevated HbA1c (6.0–6.5% (42–48 mmol/mol)). Overexpressed genes were related mainly to the unfolded protein response, whereas underexpressed genes were related to mitochondria. Our data on transcriptional changes in human islets retrieved by LCM from high-quality biopsies, as pre-diabetes progresses to established T2D, increase our understanding on how islet stress contributes to the disease development. ? 2018 The Author(s). Published with license by Taylor & Francis ? 2018, ? Marcus Lundberg, Anton Stenwall, Angie Tegehall, Olle Korsgren, and Oskar Skog.
机译:摘要:目前未知胰岛素转录模式如何随着葡萄糖新陈代谢而变化,并进展到令人兴奋的2型糖尿病(T2D)。在这项研究中,我们假设来自HBA1C水平升高但尚未被T2D诊断的供体中的胰岛,将显示在转录水平上的细胞应激迹象。激光捕获微小菌和QPCR阵列,包括与线粒体,氧化应激或展开蛋白质反应有关的330个基因,从器官供体中提取和分析HBA1C <5.5%(37mmol / mol),HBA1C升高(6.0-6.5%) (42-48mmol / mol)),高HBA1C(> 6.5%(48mmol / mol))或建立的T2D。基于所有330个基因表达的主成分分析和分层聚类显示出四种不同供体组的明显分离,表明供体间变化大于组之间的差异。然而,与来自T2D受试者的胰岛相比,44个基因在来自供体的胰岛之间的差异表达(P <0.05,假发现率<30%),与来自T2D受试者的胰岛的胰岛相比。与具有建立的T2D和升高HBA1C(6.0-6.5%(42-48mmol / mol)的供体中的供体中的对照胰岛进行差异表达12个基因。过表达基因主要涉及展开的蛋白质反应,而缺口基因与线粒体有关。我们关于LCM从高质量活检检出的人类胰岛转录变化的数据,因为糖尿病患者进展到建立的T2D,提高了对疾病发展有助于疾病发展的理解。还2018年作者。泰勒&弗朗西斯发布的牌照? 2018年,? Marcus Lundberg,Anton Stenwall,Angie Tegehall,Olle Korsgren和Oskar Skog。

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