Epigenetics of Muscle Insulin Resistance
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|ClinicalTrials.gov Identifier: NCT03259984|
Recruitment Status : Completed
First Posted : August 24, 2017
Last Update Posted : October 14, 2019
|Condition or disease|
|Diabetes Mellitus, Type 2 Obesity|
|Study Type :||Observational|
|Actual Enrollment :||72 participants|
|Official Title:||Epigenetics and the Origin of Muscle Insulin Resistance in Humans Aims 1-3|
|Actual Study Start Date :||November 2016|
|Actual Primary Completion Date :||November 2, 2018|
|Actual Study Completion Date :||November 2, 2018|
This experiment will use the next generation sequencing reduced representation bisulfite sequencing to define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers. The investigators will test the hypotheses that: (a) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (b) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (c) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.
This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that: (a) Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and (b) Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.
This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that: (a) There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes, (b) There is altered methylation of genes involved in inflammation and cytoskeletal structure.
- DNA methylation of genes in insulin resistance [ Time Frame: 9 months ]DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.
- mRNA expression of genes [ Time Frame: 9 months ]mRNA expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeletal signaling are altered in insulin resistance, with an acute episode of exercise and with 8 weeks of exercise training.
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259984
|United States, Arizona|
|University of Arizona|
|Tucson, Arizona, United States, 85724|
|Principal Investigator:||Dawn K Coletta, Ph.D.||University of Arizona|