Analysis of Inflammatory Gene Expression Profile of Peripheral Blood Leukocytes in Type 2 Diabetes

The pathophysiology of type 2 diabetes (T2DM) is associated with perturbation of innate immune response. Several studies indicated alteration of pro-inflammatory and anti-inflammatory cytokines, chemokines and other mediators of innate immune response in T2DM. This study was designed to perform quantitative PCR-based expression profiling of genes involved in inflammation (i.e. CASP1, CASP5, CCL5, CXC11, CCR5, NF-Κb, IL-4, PPARG and PGC1α) in peripheral blood leukocytes of T2DM patients. The T2DM patients are often prescribed with metformin and insulin while metformin has also been reported to possess anti-inflammatory activity. To address the question whether metformin exerts any effect on inflammatory mediators in bloodstream, human subjects in this study were divided into four groups on the basis of medication they were taking during last 6 month. These groups included NT-T2DM (T2DM patients not taking medication, n = 34), Met-T2DM (T2DM patients taking metformin, n = 33), INS-T2DM (T2DM patients taking insulin, n = 15) and NGT (normoglycemic subjects, n = 34) groups. Differential expression of gene transcripts at a cutoff of fourfold was considered significant. In the NT-T2DM group, transcripts of inflammation-related genes (i.e. CASP1, CASP5, CCL5, CCR5 and NF-kB) were up-regulated while transcripts of PPARG and PGC1α genes were down-regulated compared to NGT group. On the other hand, down-regulation of CASP1, CASP5, CCL5, CCR5 and NF-kB transcripts was evident in Met-T2DM and INS-T2DM groups when compared to the NT-T2DM group. The Met-T2DM group and INS-T2DM group showed a significant difference in the transcript level of CASP1 and CCL5 which are more down-regulated in the Met-T2DM group compared to INS-T2DM group. These findings indicated that (a) in T2DM, expression of inflammation-related genes is up-regulated and (b) anti-inflammatory activity of metformin appears to be independent of its anti-hyperglycemic activity.