Mitochondrial Dysfunction in Diabetes

NCT01724502 | Completed

• 2 other identifiers: 11-006065 Aim 4R01DK066483
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether insulin resistance is accompanied by "exercise resistance". Investigators will use mass spectrometry and proteomics analysis to test the hypothesis is that a bout of exercise that increases mitochondrial protein abundance in lean, healthy individuals is less effective in insulin resistant patients.

Conditions

Diabetes; Obese

Keywords

insulin resistance

Outcome Measures

Primary Outcomes (1)

• Protein Concentration of Mitochondria

  Protein concentration will be determined from muscle biopsies by the method of Lowry. 75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain. The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.

  Study Day 4 (30 min after exercise) and (24 hours after exercise)

Study Arms (3)

Obese Non-Diabetic Subjects

EXPERIMENTAL

All subjects on this arm will undergo exercise and muscle biopsies.

Behavioral: Exercise and muscle biopsies

Type 2 Diabetic Subjects

EXPERIMENTAL

All subjects on this arm will undergo exercise and muscle biopsies.

Behavioral: Exercise and muscle biopsies

Healthy Control Subjects

EXPERIMENTAL

All subjects on this arm will undergo exercise and muscle biopsies.

Behavioral: Exercise and muscle biopsies

Interventions

Exercise and muscle biopsies BEHAVIORAL

Subjects will undergo a euglycemic clamp, VO\_2 max determination, exercise periods and muscle biopsies.

Healthy Control Subjects; Obese Non-Diabetic Subjects; Type 2 Diabetic Subjects

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Aspartate Aminotransferase (AST) (SGOT) \< 2 times upper limit of normal
• Alanine Aminotransferase (ALT) (SGPT) \< 2 times upper limit of normal
• Alkaline phosphatase \< 2 times upper limit of normal
• Triglycerides \< 150 mg/dl.
• Prothrombin Time (PT) 11.7 -14.3 seconds (during Intralipid/heparin infusion,PT will be determined to insure that it is \< 1.5-2.0 times the normal value.)
• Partial thromboplastin time (PTT) 23.0-37.0 seconds.

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.
• 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

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus; Obesity; Insulin Resistance

Interventions

Exercise

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Lawrence Mandarino, Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D.

Study Record Dates

• First Submitted: November 7, 2012
• First Posted: November 9, 2012
• Study Start: September 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 12, 2014

Record last verified: 2014-05

Locations

US (1)