Aberrant PDK4 Promoter Methylation Preceding Hyperglycemia in a Mouse Model

Diabetic prevalence is at speedy increase globally. Previous studies stated that other than genetics, factors such as environment, lifestyle, and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome. The purpose of this study is to investigate the methylation pattern of the PDK4 promoter in streptozotocin-induced diabetic mice until the 12th week of the observation. The methylation pattern in the blood samples was analyzed periodically, while the pattern in the muscle sample was only analyzed at the end of the experiment using the blood of the sacrificed animals. Three methylated CpG site 1, CpG site 6, and CpG site 7 were analyzed and quantified based on the band density using bisulfite treatment and methylation-specific polymerase chain reaction (PCR). The hyperglycemia period was developed at the 9th week of experiment. However, there was a significant increase of methylation, specifically on CpG site 6 started from week 6 to week 12. This peculiar methylation on CpG site 6 of PDK4 promoter in the blood sample before the hyperglycemic period might serve as a potential biomarker for early detection of diabetes in the patients. No significant difference was found between the methylation level of streptozotocin (STZ)-treated mice and of the control group in the muscle sample.