Transcriptome and Proteome Expressions Involved in Insulin Resistance in Muscle and Activated T-Lymphocytes of Patients with 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 ex-pressions 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 α (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 correspond-ing to molecular weights of the above translated transcriptomes showed different patterns of changes between T2DM and controls. Meanwhile,changes in tran-scriptomes and proteomes between muscle and activated T-cells of T2DM were comparable. Activated T-cells,analogous to muscle cells,expressed insulin sig-naling 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.