目的·筛选脂蛋白脂酶（lipoprotein lipase，Lpl）基因杂合敲除（Lpl+/-）小鼠和野生型（wild type，WT）小鼠的胰岛组织中差异表达基因（differentially expressed genes，DEGs）和通路，探讨脂毒性介导2型糖尿病（type 2 diabetes mellitus，T2DM）发病过程中的分子机制。方法·将Lpl+/-小鼠和WT小鼠的胰岛进行分离纯化。通过基因芯片分析获得DEGs，并对其进行GO（Gene Ontology）功能分析和KEGG（Kyoto Encyclopedia of Genes and Genomes）通路分析。采用实时荧光定量PCR（quantitative real-time PCR，qPCR）对关键基因表达进行验证。结果·共筛选出187个DEGs。GO功能分析和KEGG通路分析显示，DEGs主要富集于免疫细胞增殖分化、炎症信号通路及细胞黏附等生物过程。在Lpl+/-小鼠和WT小鼠的表达差异最为显著的前10个基因中，gremlin 1（Grem1）基因与胰岛β细胞功能密切相关，且经qPCR验证与基因芯片的结果一致。结论·脂毒性介导T2DM的过程涉及多个信号通路的参与，其可能是通过抑制Grem1表达导致胰岛β细胞功能障碍。

Objective · To screen the differentially expressed genes (DEGs) and pathways in the islet tissues of lipoprotein lipase (Lpl) gene heterozygous knockout (Lpl+/-) mice and wild type (WT) mice, and explore the molecular mechanism of pathogenesis of type 2 diabetes mellitus (T2DM) mediated by lipotoxicity. Methods · The islets of Lpl+/- mice and WT mice were isolated and purified. DEGs were screened by gene microarray analysis. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were performed. The expressions of key genes were verified by quantitative real-time PCR (qPCR). Results · A total of 187 DEGs were identified. GO functional analysis and KEGG pathway analysis showed that DEGs were mainly involved in the biological processes such as immune cell proliferation and differentiation, inflammatory signaling pathways and cell adhesion. Among the top 10 DEGs screened from Lpl+- mice and WT mice, gremlin 1 (Grem1) gene was closely related to the function of islet β cells, while the result of qPCR was consistent with that of gene microarray analysis. Conclusion · Multiple signaling pathways are involved in the process of T2DM mediated by lipotoxicity, which may lead to the dysfunction of islet β cells by inhibiting Grem1 expression.