Molecular Regulation of Muscle Glucose Metabolism

This protocol is being conducted to determine the mechanisms responsible for insulin resistance, obesity and type 2 diabetes.

Study Overview

• Status: Terminated
• Conditions: Obesity; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: U100 Humulin; Other: Exercise

Detailed Description

This protocol involves performance of a hyperinsulinemic euglycemic clamp with 2 muscle biopsies and an exercise study with a muscle biopsy.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
2. Subjects may be of either sex, age as described in each protocol. Female subjects must be non-lactating and must either be at least two years post-menopausal, (if diabetic or obese) or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients (except for those patients who have undergone a hysterectomy or bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period.
3. Subjects must range in age as described in each specific protocol.
4. All nondiabetic subjects must have normal oral glucose tolerance.

5. Subjects must have the following laboratory values:

   1. Hematocrit ≥ 35 vol%
   2. Serum creatinine ≤ 1.6 mg/dl
   3. Aspartate aminotransferase (AST) (SGOT) < 2 times upper limit of normal
   4. Alanine aminotransferase (ALT) (SGPT) < 2 times upper limit of normal
   5. Alkaline phosphatase < 2 times upper limit of normal
   6. Triglycerides < 150 mg/dl.
   7. Prothrombin time (PT) 11.7 -14.3 (During Liposyn/heparin infusion, PT will be determined to insure that it is < 1.5-2.0 times the normal value.)
   8. Partial thromboplastin time (PTT) 23.0-37.0.

Exclusion Criteria:

1. 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 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.
2. 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.
3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; Proteomics of muscle after a single bout of exercise compared to baseline with U100 Humulin infusion at rate of 80 milliunits(mU)/m^2 surface area.	Drug: U100 Humulin; Infused at a rate of 80/mU/m2 surface area per minute one time over 2 hours; Other Names: Humulin; Human insulin; Other: Exercise; Single episode of exercise riding a stationary bike.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin sensitivity	euglycemic clamp	one month from date of volunteer study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acetylation of mitochondrial adenine nucleotide translocase	proteomics analysis of post translational modification of proteins obtained from isolated mitochondria	within 6 months of volunteer study

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Arizona State University
• Investigators: Principal Investigator: Lori Roust, MD, Mayo Clinic; Principal Investigator: Lawrence J. Mandarino, PhD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: February 15, 2012
• First Submitted That Met QC Criteria: April 18, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Actual): November 27, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: mitochondria; insulin resistance
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 11-004005