Ischemia-reperfusion Exercise Study

Insulin Sensitivity Clinical Trial

Official title:

Effect of Ischemia on the Insulin-sensitizing Effect of Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04872426
• Other study ID #: Ischemia
• Status: Completed
• Phase: N/A
• Start date: August 31, 2018
• Est. completion date: January 3, 2020

Study information

• Verified date: April 2021
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 3, 2020
• Est. primary completion date: January 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity
• Ischemia

Intervention

Other:
• Exercise, insulin infusion
Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise

Locations

Country	Name	City	State
Denmark	Department of Exercise, Nutrition and Sports, Faculty of Sciences, University of Copenhagen	København

Sponsors (1)

Lead Sponsor	Collaborator
University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle glucose uptake during exercise and enhanced insulin sensitivity in recovery from exercise.	Leg glucose uptake is calculated by the arterial-venous difference i blood glucose concentration multiplied with leg blood flow. Sampling of artery and venous blood samples for blood glucose measurements. Measures of artery blood flow by Ultrasound Doppler technique allows a final calculation of glucose uptake across the legs before exercise, during exercise, in recovery from exercise and with insulin stimulation.	Through study completion, an average of 1 year.
Secondary	AMPK activity in muscle biopsies	The obtained muscle samples will be subjected to protein kinase activity measurements.	5 years
Secondary	Posttranslational modification of proteins in muscle biopsies	The obtained muscle samples will be subjected to standard western blotting for the evaluation of posttranslational modifications of various proteins involved in glucose metabolism.	5 years