PGC-1 & Muscle Mitochondrial Dysfunction in Diabetes

Summary

The goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level.

Conditions

• Diabetes
• Obesity

Interventions

BEHAVIORAL

Pre-study dietary and exercise instruction.

All subjects will be instructed to continue their normal diet during the three days prior to study, to not consume alcohol the day before study, and to not engage in exercise for 48 hours before all studies.

PROCEDURE

Screening examination and oral glucose tolerance test

All subjects will have screening exam and OGTT at the Clinical Studies Infusion Unit at Mayo Clinic in Arizona at 7-8 am after having eaten nothing after 10 PM the night before, and have a screening examination and 75 g OGTT, as described

PROCEDURE

Euglycemic clamp

On a separate day, subjects will have a two-hour euglycemic clamp ((80 mU insulin/(m2.min)) at the Clinical Studies Unit at Mayo Clinic Arizona at 7-8 am after an overnight fast. A muscle biopsy will be taken before the insulin infusion, to serve as the resting biopsy (3). Biopsy specimens (150-300 mg) will be frozen immediately in liquid nitrogen and stored in liquid nitrogen until they are processed

PROCEDURE

VO2max.

VO2max.

BEHAVIORAL

Acute exercise bout

The single acute exercise bout will be performed as described (3). It consists of 4 sets of 12 min each (8 min @ 70% VO2max, 2 min @ 90%, 2 min rest, repeat X 4). Biopsies are taken 30 min and 24 hr after end of exercise. Resting biopsies are taken on the glucose clamp day

PROCEDURE

Percutaneous needle muscle biopsies

Skeletal muscle biopsies, blotted free from blood, are frozen within 30 seconds in liquid nitrogen, and stored in liquid nitrogen until processing. We routinely obtain 150-300 mg muscle (wet weight), which is more than sufficient for the analyses proposed, with some muscle remaining for any additional validation assays that may arise during the course of the research. Muscle will be processed either for isolation of mRNA/microRNA or protein, as described (2, 3, 12).

Sponsors & Collaborators

• Arizona State University

  collaborator OTHER

• Mayo Clinic

  lead OTHER

Principal Investigators

• Lawrence J. Mandarino, Ph.D. · Mayo Clinic

• Lori Roust, MD · Mayo Clinic

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

59 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-05-31

Primary Completion

2016-04-30

Completion

2016-04-30

Countries

• United States

Study Locations