Gene expression profiles of peripheral blood cells in type 2 diabetes and nephropathy in Asian Indians
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Asian Indians with type 2 diabetes mellitus (T2D) have higher susceptibility to diabetic nephropathy (T2DN), the leading cause of end-stage renal disease and morbidity in diabetes. Peripheral blood cells (PBCs) play an important role in diabetes, yet very little is known about the molecular mechanisms of PBCs regulated in insulin homeostasis. In this study we explored the global gene expression changes in PBCs in diabetes and diabetic nephropathy to identify the potential candidate genes and molecular networks regulated in diabetes and nephropathy.
Gene expression profiling of mRNA from PBCs from 6 diabetics with nephropathy (T2DN), 6 diabetics without nephropathy (T2D) and 6 non-diabetic subjects (C), using 13,824 human sequence verified cDNA clones revealed significant differential expression of 420 genes. Hierarchical clustering of significant genes revealed distinct gene expression signatures for diabetes and diabetic nephropathy. Functional categories distinctly regulated in T2D vs. T2DN included, cell growth and maintenance (27 vs. 7%), enzymes (10 vs. 7%) and protein synthesis (13 vs. 18%). Pathway analysis of genes in glucose and fat metabolism were unremarkable, in contrast proteasome pathway involved in protein degradation is significantly regulated in T2D vs. T2DN.
Gene expression changes in PBCs could distinguish variable diabetic states. The data provides the opportunity to explore cellular processes in PBCs that may play a role in insulin homeostasis and insulin resistance that are distinct from target tissue such as skeletal muscle and pancreas. Identification of candidate genes in peripheral blood could provide easily accessible biomarkers to monitor diabetic nephropathy.