Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state.

Physiological Reports
Yi WangKelvin P Davies

Abstract

Hyperglycemic memory is associated with several complications of diabetes. Although there is some physiological evidence that this phenomenon occurs with diabetic bladder dysfunction (DBD), there have been no studies in bladder that provide evidence of hyperglycemic memory at the molecular/biochemical level. In the present studies, we determined the effects of long-term diabetes on the metabolome of bladder detrusor in a rat model of streptozotocin-induced type-1-diabetes and the ability of insulin treatment to normalize metabolic changes. These studies demonstrated that although insulin reversed a majority of the metabolic changes caused by diabetes, with long-term diabetes there was a persistent decrease in the methylation index (indicated by a reduced ratio of S-adenosylmethionine to S-adenosyl homocysteine) after insulin treatment. We confirmed a "hypomethylated environment" develops in diabetic detrusor by demonstrating an overall reduction in methylated detrusor DNA that is only partially reversed with glycemic control. Furthermore, we confirmed that this hypomethylated environment is associated with epigenetic changes in the detrusor genome, which are again mostly, but not completely, reversed with glycemic control. Over...Continue Reading

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Methods Mentioned

BETA
acetylation
protein assay

Software Mentioned

GraphPad Prism
ImageJ
R
GraphPad
R package princomp

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