Physical Activity and Insulin Sensitivity Dynamics

ConditionInsulin Sensitivity

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexMale

Age22-35

SponsorUniversity of Copenhagen

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Healthy individuals (no known diseases)

No use of medication

Non-smokers

Male

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

One-legged-knee extensor exercise
Other intervention
1 hour of one-legged-knee-extensor exercise followed by 4 hours of rest
Insulin infusion
Procedure/Surgery
The hyperinsulinemic-euglycemic clamp is a well-established and recognized method for determining glucose uptake at a specific insulin infusion rate. It is a technique with which we have 25 years of uncomplicated experience. During the clamp, insulin (human recombinant insulin) is infused (1.42 mU/kg/min) into an arm vein (antecubital vein), while glucose (20% solution) is administered in an amount adjusted to maintain blood glucose (plasma glucose concentration) at basal levels. The amount of insulin administered raises the participant's plasma insulin concentration (blood concentration) to approximately 100 μU/mL, which is considered within the physiological range. Blood samples are collected and analyzed continuously for glucose content, allowing for the determination of glucose uptake at the whole-body level and across the legs. Later, these blood samples will also be analyzed for relevant metabolites and proteins, including insulin, to assess the metabolism of these substances.
Muscle Biopsy Medication: Lidocaine
Procedure/Surgery
During supine rest, the skin on the outer thigh, approximately 15 cm above the knee, is disinfected with chlorhexidine alcohol. Subsequently, 3-4 mL of local anesthetic (lidocaine 20 mg/mL) is administered into the skin, subcutaneous tissue, and the upper portion of the muscle using a very thin needle. A pinprick test is performed after a few minutes to ensure the anesthetic is effective. A small incision is then made in the skin and subcutaneous tissue to allow the biopsy needle to pass through to the muscle. Using the biopsy needle, a small sample of muscle tissue (approximately 150 mg) is collected. This may cause some discomfort but is very brief (\~1-2 seconds). The needle is removed, a sterile dressing is applied, and the participant can leave the facility after completing the study. The biopsy may result in mild muscle soreness for 2-3 days, similar to a minor muscle bruise. Regular physical activities can be resumed after the biopsy. However, it is advised to avoid swimming.
Exercise
Other intervention
The participants' maximal oxygen uptake is determined through a test on a cycle ergometer before the start of the experiment. The test begins with a 20-minute warm-up at two different low workloads, after which the workload is gradually increased until the predetermined cadence can no longer be maintained, or the participant indicates exhaustion. During the test, the participant's exhaled air is collected. After completing the warm-up, it typically takes between 4 and 7 minutes to complete the test.

Treatment groups

8 Participants

are divided into 1 treatment group

Group A: Post-exercise insulin sensitivityExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

Insulin stimulated muscle glucose uptake

Muscle glucose uptake during insulin stimulation in recovery from exercise (insulin sensitivity) will be determined based on Fick's principle. Thus, femoral arterio-venous difference (av difference) in blood glucose concentration will be multiplied by femoral arterial leg blood flow.

Time frame

Through study completion, approx. 1 year.

Secondary outcomes

Posttranslational modification of proteins in muscle biopsies

The obtained muscle samples will be subjected to mass spectrometry-based phosphoproteomic analysis. This measurement shows posttranslational modification that regulates protein function and will reveal the signalling network underlying the interventions studied. Unit of measure is log2-transformed arbitrary units

Time frame

3 years

Other outcomes

Imaging of transport protein

The obtained muscle samples will be subjected to a microscopy method to validate the spatial distribution and re distribution following insulin stimulation.

Time frame

1 year

Maximum oxygen uptake

The participants' maximal oxygen uptake is determined through a test on a cycle ergometer before the start of the experiment. The test begins with a 20-minute warm-up at two different low workloads, after which the workload is gradually increased until the predetermined cadence can no longer be maintained, or the participant indicates exhaustion. During the test, the participant's exhaled air is collected. After completing the warm-up, it typically takes between 4 and 7 minutes to complete the test.

Time frame

Through study completion, approx. 1 year.

Sponsors and contacts

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University of Copenhagen

Lead sponsor

Source ClinicalTrials.gov

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