Virginia Tech
Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models
Abstract
dc:description.abstractType 2 Diabetes Mellitus (T2DM), a metabolic disorder denoted by elevated blood glucose levels and insufficient insulin action, is growing in prevalence worldwide . Barriers to improving disease outcome resolve primarily around identifying and intervening during the preliminary stages of insulin resistance, a state clinically referred to as pre-diabetes. Emerging evidence suggests that mitochondrial dysfunction may underlie , and potentially precede, progressive insulin resistance, suggesting that biomarkers indicative of mitochondrial dysfunction could predict disease risk and status. In this study, we examined epigenetic modifications, in the form of DNA methylation, in the promoter region of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), a known regulator of mitochondrial biogenesis. Following the initiation of a high fat diet, we observed significant genotypic (DNA methylation) and phenotypic (mitochondrial copy number) alterations in C57/BL6 rodent models. These changes preceded overt disease onset, as classified by clinically utilized indices, which included the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as an effective clinical parameter to use in conjunction with physiological criterion for the diagnosis of pre-diabetes and the assessment of T2DM disease risk, and adds to the growing body of work seeking to elucidate the role.
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy
- Level thesis:degree_level
- doctoral
- Discipline thesis:degree_discipline
- Human Nutrition, Foods, and Exercise
- Department dc:contributor.department
- Human Nutrition, Foods and Exercise
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 2019
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Donnelly, Sarah Rebecca
- Chairs dc:contributor.committeechair
-
- Cheng, Zhiyong
- Schmelz, Eva M.
- Committee members dc:contributor.committeemember
-
- Hulver, Matthew W.
- Almeida, Fabio A.
- McMillan, Ryan P.
Subjects
dc:subject × 4Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
Identifiers
dc:identifier.*- Dc Identifier Other
- vt_gsexam:21931
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/92592