PGC-1 & MUSCLE MITOCHONDRIAL DYSFUNCTION IN DIABETES: AIMS 1-4

NCT03323788 | Unknown

• 1 other identifier: 1606632517
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle.

Conditions

Type2 Diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Response of muscle mRNA to acute exercise

  mRNA differential response in muscle to exercise in obese patients

  2014-2019

Study Arms (4)

Aim 1

Aim 1. To determine whether the transcription factor expression response to exercise is dysregulated in muscle from type 2 diabetic patients. We will test the hypothesis that MZF1, NFKB1, RELA, SP1/KLF and EGR1 responses to an acute exercise bout are reduced in insulin resistant patients with type 2 diabetes.

Aim 2

Aim 2. To determine how insulin resistance changes the response of post-translational modifications of SP1/KLF family and MZF1 transcription factors to acute exercise in muscle from type 2 diabetic patients. We will test the hypothesis that: 1. SP1/KLF2, 4, and 6 and phosphorylation/acetylation and MZF1 phosphorylation is altered in response to acute exercise. 2. The response of SP1/KLF2, 4, and 6 phosphorylation and acetylation and MZF1 phosphorylation to acute exercise is abnormal in patients with type 2 diabetes.

Aim 3

Aim 3. To define the response of miRNAs to acute exercise in healthy and insulin resistant muscle from obese and type 2 diabetic patients. We will test the hypotheses that: 1. The exercise-induced increases in expression of miR-378 members and miR-128 are lower in obese and type 2 diabetic muscle than in lean healthy controls. 2. FOXO1 expression, a target of miR-378 and miR-128, is higher in obese and type 2 diabetic muscle and this is accompanied by decreased FOXO1 phosphorylation. 3. The exercise-induced increases in expression of miR-30 family members, miR-10a, miR-422a, and miR-532 are lower in obese and type 2 diabetic muscle. 4. There are novel miRNAs that regulate the transcriptional program induced by acute exercise and are dysregulated in insulin resistance.

Aim 4

Aim 4. To determine whether treatment with PPAR-Alpha agonist fibrate derivatives suppresses the normal gene expression response to acute exercise. We will test the hypothesis that Gemfibrozil treatment inhibits the normal transcriptional response to exercise.

Eligibility Criteria

• Age: 30 Years - 59 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The plan is to have about 84 people take part in aims 1 to 3 and about 12 people in aim 4. Adults between the ages of 30 - 59 may participate.

You may not qualify if:

• \. 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 sectretion.
• \. Subjects receiving Gemfibrozil must not also be receiving a statin. 3. 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.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

The University of Arizona

Tucson, Arizona, 85724, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lawrence Mandarino, PHD

  The University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oscar D Parra, MADM

CONTACT

520-626-6485; oscardp@email.arizona.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: October 27, 2017
• Study Start: November 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 27, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)