Transcriptome and Proteome Expressions Involved in Insulin Resistance in Muscle and Activated T-Lymphocytes of Patients with Type 2 Diabetes

作     者：Frankie B.Stentz Abbas E.Kitabchi 

作者机构：Division of EndocrinologyDiabetes and MetabolismDepartment of MedicineThe University of Tennessee Health Science CenterMemphisTN 38163USA. 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2007年第5卷第3期

页      面：216-235页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 0714[理学-统计学（可授理学、经济学学位）] 0703[理学-化学] 0701[理学-数学] 0812[工学-计算机科学与技术（可授工学、理学学位）] 10[医学] 

基　　金：National Center for Research Resources,NCRR: M01RR000211 U.S. Public Health Service,USPHS 

主　　题：genomics proteomics T-lymphocytes activation muscle Type 2 diabetes 

摘      要：We analyzed the genes expressed （transcriptomes） and the proteins translated （pro- teomes） in muscle tissues and activated CD4^＋ and CD8^＋ T-lymphocytes （T-cells） of five Type 2 diabetes （T2DM） subjects using Affymetrix microarrays and mass spectrometry, and compared them with matched non-diabetic controls. Gene expressions of insulin receptor （INSR）, vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 （IRS-1）, IRS-2, glucose transporter 4 （GLUT4）, and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls. However, there was greater than two-fold gene upregulation of plasma cell glycoprotein-1, tumor necrosis factor a （TNFα）, and gluconeogenic enzymes in T2DM than in controls. The gene silencing for INSR or TNFα resulted in the inhibition or stimulation of GLUT4, respectively. Proteome profiles corresponding to molecular weights of the above translated transcriptomes showed different patterns of changes between T2DM and controls. Meanwhile, changes in transcriptomes and proteomes between muscle and activated T-cells of T2DM were comparable. Activated T-cells, analogous to muscle cells, expressed insulin signaling and glucose metabolism genes and gene products. In conclusion, T-cells and muscle in T2DM exhibited differences in expression of certain genes and gene products relative to non-diabetic controls. These alterations in transcriptomes and proteomes in T2DM may be involved in insulin resistance.