The effect of diet-induced insulin resistance on DNA methylation o. The androgen receptor promoter i. The penile cavernosal smooth muscle of mice

Abstract

Population studies have suggested an association between diabetes an. The symptoms of testosterone deficiency. Recently. The expression o. The androgen receptor (AR) has been shown to be decreased in diabetic patients. Furthermore, diabetes has been shown to induce global methylation. In this study, we used an animal model to investigate whether diabetes results in increased methylation o. The AR promoter and whether these changes are associated wit. The decreased expression of AR in penile cavernosal smooth muscle tissue. Twenty C57BL/6J mice were divided into two groups, receiving either high- (mature diabetic) or low- (mature control) caloric meals for 14 weeks. Another 10 mice were killed at 1 week (young control). Animals i. The mature diabetic group showed decreased testosterone levels, although this was not statistically significant. In both control groups, no significant methylation was observed i. The AR promoter region CpG island (-85 to +339). I. The mature diabetic group, significant methylation was observed at +185 and +200 o. The AR promoter. These changes were associated with increased homeostatic model assessment for insulin resistance (HOMA-IR) and decreased corpus cavernosal tissue mass and expression of AR mRNA and protein. We conclude that in these animals, insulin resistance increase. The methylation o. The GC-rich regions o. The AR promoter, leading to decreased AR expression.