Clinical trial NCT06776094: Physical Activity and Insulin Sensitivity Dynamics
Official title: The Significance of Physical Activity for Insulin Signaling Dynamics and Insulin Sensitivity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insulin Sensitivity
Keywords: Exercise
Muscle insulin sensitivity
Muscle glucose uptake
GLUT4
Phosphoproteomics
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
First posted: 2025-01-15
Enrollment: 8
Sex: MALE
Minimum age (years): 22
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The study investigates the role of one single bout of exercise in mediating enhancement of muscle insulin sensitivity following a single bout of exercise. Furthermore, the study is aiming to elucidate the temporal development in insulin signaling, at the early timepoints of insulin stimulation that may be responsible for the enhanced muscle insulin sensitivity.

This will be investigated in young healthy males subjected to a one-legged knee-extensor exercise followed by a hyperinsulinemic-euglycemic clamp, a setup known to enhance muscle insulin sensitivity.

Detailed description: The participant arrives fasting at 8:00 AM, having abstained from alcohol, nicotine, and caffeine for the past 24 hours and refrained from strenuous physical activity for the past 48 hours. The participants are then subjected to a one-legged knee extension exercise performed by the participant from 9:00 AM to 10:00 AM.

Groin catheters are inserted into the femoral artery and vein using ultrasound guidance and sterile technique

Two hours after the completion of the exercise, a catheter is inserted into an arm vein (antecubital vein) and groin catheters are inserted into the femoral artery and vein using ultrasound guidance and sterile technique. Four hours after the exercise ends, a hyperinsulinemic-euglycemic clamp is commenced. The clamp begins with a bolus injection of insulin, followed by a continuous infusion. Glucose is infused concurrently to maintain constant blood glucose levels.

Throughout the procedure, blood samples are collected every 5 minutes from the femoral catheters, and blood flow is measured using ultrasound Doppler. Muscle biopsies from the vastus lateralis of both legs are taken before the clamp starts and at 3, 6, 10, and 20 minutes after the clamp's initiation. Following the 20-minute mark, the clamp continues until steady-state is achieved to determine tissue-specific and whole-body insulin sensitivity.

Over the course of the experiment, a total of 10 muscle biopsies and approximately 150 mL of blood are collected. The experimental part of the study is expected to conclude by 4:30 PM. Participants are provided with food and beverages and observed for 1 hour before being allowed to leave the research laboratory.

Eligibility criteria: Inclusion Criteria:

* Healthy individuals (no known diseases)
* No use of medication
* Non-smokers
* Male
* Aged 22-35 years
* Fitness level (VO2max, i.e., maximal oxygen uptake) between 30-50 mL O2/min/kg
* BMI between 28 and 35

Exclusion Criteria:

* Women
* Failure to meet all inclusion criteria
* Physical activity level (e.g., running, cycling, fitness, etc.) exceeding 6 hours per week
* Acute illness within 2 weeks prior to the study days
* Use of recreational drugs within 2 weeks prior to the study days

Primary outcomes:
measure: Insulin stimulated muscle glucose uptake
timeFrame: Through study completion, approx. 1 year.
Secondary outcomes:
measure: Posttranslational modification of proteins in muscle biopsies
timeFrame: 3 years
Other outcomes:
measure: Imaging of transport protein
timeFrame: 1 year
measure: Maximum oxygen uptake
timeFrame: Through study completion, approx. 1 year.
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen, August Krogh Section for Human and Molecular Physiology
Study officials:
affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
name: Jørgen FP Wojtaszewski, Prodessor
role: PRINCIPAL_INVESTIGATOR
References: