Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state
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/...
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Wiley
2020-11-01
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| Online Access: | https://doi.org/10.14814/phy2.14614 |
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| author | Yi Wang Moses T. Tar Kelvin P. Davies |
| author_facet | Yi Wang Moses T. Tar Kelvin P. Davies |
| author_sort | Yi Wang |
| collection | DOAJ |
| description | 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. Overall our studies provide strong molecular evidence for a mechanism by which diabetes alters methylation status and gene expression in the detrusor genome, and that these epigenetic modifications contribute to hyperglycemic memory. Our work suggests novel treatment strategies for diabetic patients who have attained glycemic control but continue to experience DBD. For example, epigenomic data can be used to identify “actionable gene targets” for its treatment and would also support a rationale for approaches that target the hypomethylation index. |
| format | Article |
| id | doaj-art-92ecfebf38314f448858525088999217 |
| institution | DOAJ |
| issn | 2051-817X |
| language | English |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-92ecfebf38314f4488585250889992172025-08-20T03:14:31ZengWileyPhysiological Reports2051-817X2020-11-01822n/an/a10.14814/phy2.14614Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated stateYi Wang0Moses T. Tar1Kelvin P. Davies2Department of Urology Albert Einstein College of Medicine Bronx NY USADepartment of Urology Albert Einstein College of Medicine Bronx NY USADepartment of Urology Albert Einstein College of Medicine Bronx NY USAAbstract 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. Overall our studies provide strong molecular evidence for a mechanism by which diabetes alters methylation status and gene expression in the detrusor genome, and that these epigenetic modifications contribute to hyperglycemic memory. Our work suggests novel treatment strategies for diabetic patients who have attained glycemic control but continue to experience DBD. For example, epigenomic data can be used to identify “actionable gene targets” for its treatment and would also support a rationale for approaches that target the hypomethylation index.https://doi.org/10.14814/phy2.14614detrusordiabetic bladder dysfunctionepigeneticshyperglycemic memorymetabolismmetabolomics |
| spellingShingle | Yi Wang Moses T. Tar Kelvin P. Davies Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state Physiological Reports detrusor diabetic bladder dysfunction epigenetics hyperglycemic memory metabolism metabolomics |
| title | Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| title_full | Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| title_fullStr | Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| title_full_unstemmed | Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| title_short | Hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| title_sort | hyperglycemic memory in the rat bladder detrusor is associated with a persistent hypomethylated state |
| topic | detrusor diabetic bladder dysfunction epigenetics hyperglycemic memory metabolism metabolomics |
| url | https://doi.org/10.14814/phy2.14614 |
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