DNA Microarray Analysis of Type 2 Diabetes-Related Genes Co-regulated between White Blood Cells and Livers of Diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Abstract

In a previous study, we hypothesized that some type 2 diabetes mellitus susceptible genes may be up/down-regulated in white blood cells (WBC) of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, reflecting their up/down-regulation in major insulin-target tissues such as the liver before the onset of diabetes. We identified 57 potential candidate genes for predicting diabetes. In this study, we examined this hypothesis further by extending the experimental conditions from before the onset (6 weeks) to after the onset (24 weeks) of diabetes that type 2 diabetes mellitus susceptible genes are co-regulated in WBC, reflecting their expression in the liver. Using rat oligo DNA microarrays, we found that 48 genes are up/down-regulated in OLETF rats compared to control Long-Evans Tokushima Otsuka (LETO) rats in WBC and liver under fasting or insulin administration conditions. Twenty nine and 33 genes were up/down-regulated in both WBC and livers, respectively, under fasting and insulin administration conditions, respectively. Eight out of 29 genes in fasting condition and 12 out of 33 genes in insulin administration conditions have been reported to be type 2 diabetes mellitus susceptible genes and the remainder have not been reported to be related to type 2 diabetes mellitus. These results support our hypothesis that the expression levels of type 2 diabetes mellitus related genes in WBC are reflective of those in the liver after the onset of diabetes.