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/downregulated 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.

BSTA Promotes mTORC2-Mediated Phosphorylation of Akt1 to Suppress Expression of FoxC2 and Stimulate Adipocyte Differentiation

“…5A). These data are consistent with previous findings indicating that phosphorylation of Akt increases during adipocyte differentiation (20) and that BSTA amounts are increased in human skeletal muscle by insulin treatment (29) and are higher basally in adipose and liver tissue in ob/ob obese mice (30). To determine whether BSTA had a function in adipogenesis, we knocked it down in 3T3 L1 preadipocytes before inducing differentiation.…”

Gene Expression Profiling in Peripheral White Blood Cells in Response to the Intake of Food with Different Glycemic Index Using a DNA Microarray

“…Blood, which is the most readily accessible cellular material in human intervention studies, interacts with every organ and tissue in the body and has crucial roles in immunity and inflammation. It has been reported that the expression of some genes in the peripheral white blood cells (WBC) reflects their expression in the liver, one of the major insulin target tissues, although blood is not a major insulin target tissue [9,10]. Some studies have shown that gene expression in the WBC may reflect nutrition-related metabolic changes such as fasting and differences in the macronutrient content or the fatty acid composition [11,12,13,14].…”

Reduced Plasma Glucose by Asparagine Synthetase Knockdown in the Mouse Liver

“…7,[11][12][13] It would be interesting to examine whether change in expression is a cause or result of (pre-) diabetic state, for each gene. Detailed analyses of these genes, as well as the Asns gene, would help us understand the molecular mechanisms associated with the onset of T2DM, develop diagnostic tools for T2DM before onset, and establish fundamental therapies for the disease.…”