Gene expression profiles of Beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes.
Gene expression profiles of Beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes.
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DOI：
10.1371/journal.pone.0011499
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发表时间：
2010-07-13
期刊：
影响因子：
3.7
通讯作者：
Weir GC
中科院分区：
文献类型：
--
作者：
Marselli L;Thorne J;Dahiya S;Sgroi DC;Sharma A;Bonner-Weir S;Marchetti P;Weir GC
来自2型糖尿病（T2D）的胰腺β细胞中基因表达的变化应该提供对其异常胰岛素分泌和周转的见解。从10名对照和10名T2D人类受试者的尸体胰腺获得冷冻切片。通过激光捕获显微切割（LCM）获得β细胞富集的样品。提取RNA，扩增并进行微阵列分析。用DNA芯片分析仪（dChip）和基因集富集分析（GSEA）软件进行进一步分析。与葡萄糖毒性相关的基因表达发生了变化。氧化应激的证据是由几个金属硫蛋白基因的上调。与细胞周期、凋亡或内质网应激相关的主要基因变化较少。与胰腺再生相关的基因有差异表达，最明显的是再生胰岛基因（REG）家族和金属蛋白酶7（MMP 7）的成员上调。在GWAS研究中发现的与T2D相关的一些基因也被发现差异表达。IGF2BP2、TSPAN 8和HNF1B（TCF 2）上调，而JAZF 1和SLC 30A8下调。LCM使这项研究成为可能，已经确定了许多新的基因表达变化，增强了对T2D发病机制的理解。
Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover. Frozen sections were obtained from cadaver pancreases of 10 control and 10 T2D human subjects. Beta-cell enriched samples were obtained by laser capture microdissection (LCM). RNA was extracted, amplified and subjected to microarray analysis. Further analysis was performed with DNA-Chip Analyzer (dChip) and Gene Set Enrichment Analysis (GSEA) software. There were changes in expression of genes linked to glucotoxicity. Evidence of oxidative stress was provided by upregulation of several metallothionein genes. There were few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress. There was differential expression of genes associated with pancreatic regeneration, most notably upregulation of members of the regenerating islet gene (REG) family and metalloproteinase 7 (MMP7). Some of the genes found in GWAS studies to be related to T2D were also found to be differentially expressed. IGF2BP2, TSPAN8, and HNF1B (TCF2) were upregulated while JAZF1 and SLC30A8 were downregulated. This study made possible by LCM has identified many novel changes in gene expression that enhance understanding of the pathogenesis of T2D.
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