Epigenetics and the Origin of Muscle Insulin Resistance in Humans
Verified October 2016 by Mayo Clinic
Information provided by (Responsible Party):
Lori R. Roust, Mayo Clinic
First received: November 8, 2012
Last updated: October 27, 2016
Last verified: October 2016
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
||Observational Model: Cohort
Time Perspective: Prospective
||Epigenetics and the Origin of Muscle Insulin Resistance in Humans
Primary Outcome Measures:
- DNA methylation of genes in insulin resistance [ Time Frame: Baseline to visit 33 (approx 2 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.
Biospecimen Retention: Samples With DNA
Secondary Outcome Measures:
- mRNA expression of genes [ Time Frame: Baseline to visit 33 approx 2 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.
thigh muscle biopsies bloodsamples
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| 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
- Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and
- Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.
Eight weeks of exercise
This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
- 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,
- There is altered methylation of genes involved in inflammation and cytoskeletal structure.
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.
|Ages Eligible for Study:
||21 Years to 55 Years (Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2)obese volunteers without type 2 diabetes, and 3) volunteers with type 2 diabetes.
Volunteers must be:
- 21 - 55 years old
- must be non-lactating, non-pregnant
- not taking medications known to affect glucose or if taking them, on stable doses.
- free of significant heart or lung disease
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01726491
||Lori Roust, MD
||Dawn K Coletta, Ph.D.
||Lori R. Roust, Consultant in Endocrinology, Mayo Clinic
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 8, 2012
||October 27, 2016
Keywords provided by Mayo Clinic:
Type 2 diabetes mellitus
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on January 19, 2017
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Endocrine System Diseases
Insulin, Globin Zinc
Physiological Effects of Drugs