Epigenetics and the Origin of Muscle Insulin Resistance in Humans
The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a normal chemical process in the body that modifies DNA. By studying this, the investigators hope to better understand the causes of insulin resistance.
Diabetes Mellitus Type 2 in Obese
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Epigenetics and the Origin of Muscle Insulin Resistance in Humans|
- DNA methylation of genes in insulin resistance [ Time Frame: Baseline to visit 33 (approx 2 months) ] [ Designated as safety issue: No ]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: Baseline to visit 33 approx 2 months ] [ Designated as safety issue: No ]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
thigh muscle biopsies bloodsamples
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Insulin resistance epigenetics
This experiment will use the Infinium methylation assay to perform epigenome mapping and 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. We will test the hypotheses that
(1) 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, (2) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (3) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.
Single bout of exercise
This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
Eight weeks of exercise
This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
Insulin resistance is defined as the decreased ability of insulin to perform its biological function in the muscle, liver and fat. Genetic and environmental factors are known to influence insulin sensitivity. It is not known how this is mediated. This study looks at the role of epigenetics (modifications of proteins associated with DNA and methylation of DNA) in alterations in insulin resistance. We will study lean healthy people, obese non-diabetic people and people with type 2 diabetes to characterize the DNA methylation patterns in muscle in each group. The second aim of the study is to see how a single bout of exercise affects the DNA methylation in the muscle. The third aim looks at the effect of 8 weeks of supervised exercise on the DNA methylation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01726491
|Contact: Charlene Robinson||480-301-4626||ARZClinicalStudies@mayo.edu|
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Charlene Robinson 480-301-4626 ARZClinicalStudies@mayo.edu|
|Principal Investigator:||Lori Roust, MD||Mayo Clinic|
|Principal Investigator:||Dawn K Coletta, Ph.D.||Mayo Clinic|