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Epigenetics and the Origin of Muscle Insulin Resistance in Humans

2018年1月11日 更新者：Lori R. Roust、Mayo Clinic
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.

研究概览

地位

完全的

条件

详细说明

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.

研究类型

观察性的

注册 (实际的)

46

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Arizona
      • Scottsdale、Arizona、美国、85259
        • Mayo Clinic in Arizona

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

21年 至 55年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

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.

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 观测模型：队列
  • 时间观点：预期

队列和干预

团体/队列
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

  1. Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and
  2. 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

  1. 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,
  2. There is altered methylation of genes involved in inflammation and cytoskeletal structure.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
DNA methylation of genes in insulin resistance
大体时间：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.
Baseline to visit 33 (approx 2 months)

次要结果测量

结果测量
措施说明
大体时间
mRNA expression of genes
大体时间：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.
Baseline to visit 33 approx 2 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Mayo Clinic

调查人员

  • 首席研究员：Lori Roust, MD、Mayo Clinic
  • 首席研究员：Dawn K Coletta, Ph.D.、Mayo Clinic

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年8月1日

初级完成 (实际的)

2016年11月21日

研究完成 (实际的)

2016年11月21日

研究注册日期

首次提交

2012年11月8日

首先提交符合 QC 标准的

2012年11月9日

首次发布 (估计)

2012年11月15日

研究记录更新

最后更新发布 (实际的)

2018年1月16日

上次提交的符合 QC 标准的更新

2018年1月11日

最后验证

2018年1月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 11-007028

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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