Ischemia-reperfusion Exercise Study
Condition: Insulin Sensitivity
MeSH terms: Insulin Resistance; Hypersensitivity; Ischemia
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Exercise, insulin infusion
Intervention type(s): Other
Intervention description(s): Acute one-legged exercise, Insulin infusion 3 hours after one-legged exercise
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Exercise; Glucose Uptake; Ischemia; Insulin Sensitivity