Ischemia-reperfusion Exercise Study

University of Copenhagen

Status: Completed

Conditions: Insulin Sensitivity

Treatments: Other: Exercise, insulin infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04872426

Ischemia

Details and patient eligibility

About

The study investigates the relationship between activation of AMP-activated protein kinase (AMPK) in human skeletal muscle and the subsequent improvement in muscle insulin sensitivity for the stimulation of glucose uptake.

This will be investigated in young healthy lean male subjects.

Full description

This study aims to demonstrate the association between AMPK activation and increased insulin sensitivity in human skeletal muscle. The investigators intend to examine insulin sensitivity after various levels of AMPK activation in skeletal muscle that includes exercise at different intensities as well as exercise combined with leg blood flow restriction (ischemia). The hypothesis is that exercise combined with ischemia will result in an increased activation of AMPK compared to exercise alone, and therefore it is expected that exercise combined with ischemia will result in the greatest improvement in muscle insulin sensitivity.

Methods:

The main experiment consists of 3 experimental days (A, B and C), separated by a minimum of 14 days and carried out in a randomised order. On all the study days, the participants will arrive in the laboratory after an overnight fast. Catheters will be placed in both femoral veins and in one femoral artery. A muscle biopsy will be obtained from vastus lateralis of one leg (resting leg). Experiment A consists of one-legged muscle work for 1 hour at 70% of the leg maximum aerobic work capacity with the other leg serving as a resting control. In experiment B, the same work are performed, but with periodic at the same constricting the blood supply to the working leg (25 seconds every 2 min). Experiment C consists of one-legged muscle work for 1 hour at 70% and 95% of the leg maximum aerobic work capacity (alternately every 5 min). Immediately after each type of exercise a biopsy will be obtained from the exercising leg and the participants will rest in the fasted state for 3 hours before a third set of muscle biopsies (from both legs) will be obtained. Subsequently, insulin sensitivity will be evaluated in the participants during a 2-hour physiological hyperinsulinemic euglycemic clamp. By the end of the clamp, a final set of biopsies (both legs) will be obtained. Throughout the study day sampling of artery and venous blood/plasma samples allows for the estimation of substrate extraction by the two legs. Further, measures of artery blood flow by Ultrasound Doppler technique allow for the final calculation of substrate uptake/release across the two legs before exercise, during exercise and in recovery from exercise. Importantly, the ability for insulin to stimulate these processes can be evaluated in both a rested and in a prior exercised leg.

Enrollment: 10 patients

Sex: Male

Ages: 25 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• normal weight (BMI: below or equal to 27)
• physical active on a regular basis
• cardiorespiratory fitness between 40-60 ml/kg/min
• no history or sign of type 2 diabetes, hypertension, insulin resistance or dyslipidemia

Exclusion criteria

• smoker
• BMI: above 27
• using any kind of medication

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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10 participants in 3 patient groups

Low intensity exercise

Experimental group

Description:

70% of maximal leg work load capacity

Treatment:

Other: Exercise, insulin infusion

High intensity exercise

Experimental group

Description:

70% and 95% of maximal work load capacity (alternately every 5 min)

Treatment:

Other: Exercise, insulin infusion

Low intensity exercise + intermittent ischemia-reperfusion

Experimental group

Description:

70% of maximal leg work load capacity with intermittent ischemia (25 seconds every 2 min)

Treatment:

Other: Exercise, insulin infusion