Epigenetics of Muscle Insulin Resistance
11 oktober 2019 bijgewerkt door: Dawn K Coletta, University of Arizona
Epigenetics and the Origin of Muscle Insulin Resistance in Humans Aims 1-3
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.
Studie Overzicht
Toestand
Voltooid
Conditie
Gedetailleerde beschrijving
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.
The investigators 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.
Studietype
Observationeel
Inschrijving (Werkelijk)
72
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Arizona
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Tucson, Arizona, Verenigde Staten, 85724
- University of Arizona
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
21 jaar tot 55 jaar (Volwassen)
Accepteert gezonde vrijwilligers
Ja
Geslachten die in aanmerking komen voor studie
Allemaal
Bemonsteringsmethode
Niet-waarschijnlijkheidssteekproef
Studie Bevolking
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
Beschrijving
Inclusion Criteria
- Age 21-55
- BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30- 50; type 2 diabetic, BMI between 30- 50.
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- Subjects must range in age as described in each specific protocol.
Subjects must have the following laboratory values:
- Hematocrit ≥ 35 vol%
- Serum creatinine ≤ 1.6 mg/dl
- AST (SGOT) < 2 times upper limit of normal
- ALT (SGPT) < 2 times upper limit of normal
- Alkaline phosphatase < 2 times upper limit of normal
- Triglycerides < 150 mg/dl for nondiabetics
- Triglycerides <300 for diabetics
- INR ≤ 1.3
Exclusion Criteria
- Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin secretion.
- Subjects receiving Gemfibrozil must not also be receiving a statin.
- Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
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Aim 1
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.
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Aim 2
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.
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Aim 3
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.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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DNA methylation of genes in insulin resistance
Tijdsspanne: 9 months
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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.
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9 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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mRNA expression of genes
Tijdsspanne: 9 months
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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.
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9 months
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Dawn K Coletta, Ph.D., University of Arizona
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
1 november 2016
Primaire voltooiing (Werkelijk)
2 november 2018
Studie voltooiing (Werkelijk)
2 november 2018
Studieregistratiedata
Eerst ingediend
21 augustus 2017
Eerst ingediend dat voldeed aan de QC-criteria
23 augustus 2017
Eerst geplaatst (Werkelijk)
24 augustus 2017
Updates van studierecords
Laatste update geplaatst (Werkelijk)
14 oktober 2019
Laatste update ingediend die voldeed aan QC-criteria
11 oktober 2019
Laatst geverifieerd
1 oktober 2019
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 1612045470
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
NEE
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Nee
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
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