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目的 :探讨2型糖尿病家族史与胰岛素抵抗间的关系,采用信息学方法对从基因表达库(Gene Expression Omnibus,GEO)获取的具有2型糖尿病家族史但自身血糖正常的研究对象进行相关基因表达谱分析,识别2型糖尿病疾病风险通路,并对关键基因产物进行功能分析。方法:对美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)的综合性基因表达与杂交阵列数据库中26名有2型糖尿病家族史但自身血糖正常的研究对象和15名无糖尿病家族史的血糖正常的人群进行数据分析(GSE25462),运用Bergman微小模型技术结合静脉糖耐量试验评估胰岛素敏感指数,并对骨骼肌细胞基因表达谱芯片采用生物信息学方法(基因功能富集分析方法、风险通路识别方法等)进行数据分析,进而在分子层面进行2型糖尿病致病机制研究。结果:有2型糖尿病家族史但自身血糖正常的研究对象其胰岛素敏感性下降41%(P<0.05)。通过差异表达分析,共发现202个基因表达在家族史阳性组与家族史阴性组间的差异有统计学意义,同时鉴定了富集差异显著的5条通路,分别是多能干细胞的造血功能、万能干细胞的造血功能、JAK1/3在c-细胞活素信号通路的作用、TOB在T细胞信号通路中的抗增殖作用、B细胞的发育。结论 :有2型糖尿病家族史但自身血糖正常的研究对象存在胰岛素抵抗,2型糖尿病的致病机制与造血干细胞功能及免疫状态有重要联系。
OBJECTIVE: To investigate the relationship between family history of type 2 diabetes and insulin resistance and to investigate the relationship between insulin resistance and family history of type 2 diabetes using Gene Expression Omnibus (GEO) Spectrum analysis identifies the pathways of type 2 diabetes disease risk and performs functional analyzes of key gene products. Methods: Twenty-six subjects with a family history of type 2 diabetes but with normal glucose tolerance in the National Center for Biotechnology Information (NCBI) comprehensive gene expression and hybridization database and 15 non-diabetic family history (GSE25462). Bergman microscopic model and intravenous glucose tolerance test were used to evaluate the insulin sensitivity index. The gene expression microarray of skeletal muscle cells was analyzed by bioinformatics method (gene enrichment assay, risk Pathway identification methods, etc.) for data analysis, and then at the molecular level for the pathogenesis of type 2 diabetes mellitus. RESULTS: Subjects with a family history of type 2 diabetes but who had normal glucose levels had a 41% (P <0.05) decrease in insulin sensitivity. By differential expression analysis, a total of 202 gene expression was found in the family history-positive group and family history negative group was statistically significant difference, and identified five enrichment significant pathways, namely pluripotent stem cells hematopoietic function, The hematopoietic function of pluripotent stem cells, the role of JAK1 / 3 in the c-cell activin signaling pathway, the antiproliferative effect of TOB in T cell signaling and the development of B cells. CONCLUSION: There is insulin resistance in subjects with family history of type 2 diabetes but with normal blood glucose level. The pathogenesis of type 2 diabetes is closely related to hematopoietic stem cell function and immune status.