Dose-response Relationship Between Exercise and Health Outcomes
Condition: Mitochondrial Function; Glucose Intolerance
MeSH terms: Glucose Intolerance
Study type: Interventional

Summary: 
      In this study 11 healthy volunteers will perform high intensity exercise training during 4
      weeks. The exercise frequency will increase progressively during the first three weeks,
      followed by a fourth week with lower exercise frequency. 5 skeletal muscle biopsies will be
      donated throughout the study and 4 oral glucose tolerance tests will be performed after each
      training period.
    

Detailed description: 
      11 healthy and recreational active subjects will be recruited to the study. For inclusion and
      assessment of baseline physiological characteristics during cycling, a pre-test will be
      performed on a cycle ergometer and the submaximal and maximal response to exercise will be
      determined by measurement of respiratory gas exchange. The physiological response to
      submaximal work rate will be comprised of a series of five minutes long intervals separated
      with one minutes of rest with assessment of capillary blood lactate and glucose at the end of
      each workload. All physiological tests and training (HII) sessions will be carefully
      supervised by trained personnel. The intervention period will include 14 HIIT-sessions in
      total, all performed at the laboratory under close surveillance and careful monitoring of
      power output and heart rate. During HIIT sessions, VO2, CO2, blood glucose, lactate and
      rating of perceived exhaustion (BORG) will be measured.

      Energy intake will be standardized for each subject during the day of test sessions. After
      each HIIT-session a recovery drink containing 1 g · kg-1 bw of carbohydrates and 0.25 g ·
      kg-1 bw of protein will be ingested by the subjects. After HIIT sessions, subjects will be
      supplied with an evening meal consisting of 74 g carbohydrates, 38 g protein and 26 g fat to
      be consumed two hours post exercise. Subjects will thereafter remain fasted until the next
      morning for an oral glucose tolerance test (OGTT) and donation of a muscle biopsy.

      All biopsies will be collected in fasted state in early morning following 14 hour of rest
      after the last HIIT-session. Biopsies will be taken from vastus lateralis in alternating leg
      in randomized order.

      Each subject will complete four OGTTs throughout the study. Resting metabolic rate (RMR) will
      be measured in supine position by gas exchange measurement using mixing chamber method
      (Oxycon Pro) attached to a ventilated hood. Thereafter the muscle biopsy will be taken and a
      catheter will be inserted into the antecubital vein of the forearm. After 10 minutes of
      passive rest 75 mg glucose dissolved in 300 ml water will be ingested and at 0, 15, 30, 45,
      60 75, 90, 105- and 120-minutes after glucose intake a venous blood sample will be taken and
      instantly analyzed for glucose with enzymatic method in the Biosen C-Line Clinic. Additional
      RMR measurements will be performed at ~40 and 115 minutes after glucose ingestion.

      Mitochondria will be isolated from fresh skeletal muscle biopsies. Mitochondrial respiration
      and H2O2 emission will be measured using a two-channel high-resolution respirometer with an
      attached fluorescent probe (Oxygraph-2k, Oroboros Instruments Corporation, Innsbruck,
      Austria).
    

Intervention name(s): Exercise
Intervention type(s): Other
Intervention description(s): Progressively increasing training load
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science