Copenhagen, Boston, Sydney
Condition: Insulin Resistance; Insulin Sensitivity; Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2; Insulin Resistance; Hypersensitivity
Study type: Interventional

Summary: 
      The study investigates the regulation of muscle glucose utilization during exercise and
      enhanced insulin sensitivity in recovery from exercise.

      This will be investigated in lean control subjects and obese insulin resistant subjects.
    

Detailed description: 
      The subjects will perform two trials (trial A and B).

      Trial A: During trial A the study subject will eat a morning meal at 6:00 a.m. corresponding
      to 5% of the daily energy requirements and will arrive at the research laboratory at 8:00
      a.m. It is requested that the study subject will arrive in a car or with public
      transportation. After arrival the study subject will rest for 1 hour and at that time
      catheters are inserted in both femoral veins and the femoral artery in one of the legs. At
      9:00 a.m. the study subjects will perform one-leg knee extension exercise for 1 hour at an
      intensity of 80% of maximal work capacity. In this work protocol there are inserted 3
      intervals of 5 minutes duration where the study subject works at 100% of maximal intensity
      with the purpose of securing a full activation/recruiting of all muscle fibers. Muscle
      biopsies from the m. vastus lateralis muscle in both legs will be taken before (at 8.45
      a.m.), immediately after (at 10:00 a.m.) and 2 hours after conclusion of exercise (at 12:00
      p.m.) (in total of 6 biopsies). Pulmonary oxygen uptake is measured with the use of an online
      system before, during and after exercise and is used for determination of substrate
      metabolism. Blood samples from the femoral veins in both legs and the femoral artery in one
      of the legs are drawn before (at 8:20 a.m., 8:40 a.m. and 9:00 a.m.), during exercise (at
      9:20 a.m., 9:40 a.m. and 10:00 a.m.) and during the recovery period after exercise (at 10:10
      a.m., 10:30 a.m., 11:00 a.m., 11:30 a.m. and 12:00 p.m.). At the same time blood flow is
      measured in the femoral arteries in both legs with the use of Doppler technique.
      Determination of arteriovenous difference (AV difference) by simultaneous measurement of
      blood flow enables us to calculate skeletal muscle glucose uptake and uptake/release of
      relevant substances (proteins, peptides and metabolites etc.). The experimental part of trial
      A is completed at 12:00 p.m. The study subject will be given food and drink and will be
      observed for one hour before they may leave the research laboratory.

      Trial B: During test trial B the study subjects will eat a morning meal at 6:00 a.m.
      corresponding to 5% of the daily energy requirements and will arrive at the research
      laboratory at 8:00 a.m. It is requested that the study subject will arrive in a car or with
      public transportation.

      During trial B the study subjects will perform the same one-leg knee extension exercise
      protocol as in trial A. At 9:00 a.m. the study subject starts performing one-leg knee
      extension exercise for 1 hour at 80% of maximal work capacity with 3 intervals of 5 minutes
      duration where the load is at 100% of maximal work capacity. This work protocol ensures full
      activation/recruiting of all muscle fibers. After the kicking exercise is completed the study
      subject will rest in supine position for 6 hours. At the beginning of this resting period
      catheters are inserted in the femoral veins in both legs and in the femoral artery in one
      leg. Also catheters are inserted in each forearm vein (antecubital veins) for intravenous
      infusion of insulin, glucose and stable 13C(u)-glucose. Intravenous infusion of
      13C(u)-glucose is started 2 hours after conclusion of exercise in order to achieve a 10%
      enrichment of blood glucose. 4 hours after cessation of exercise a hyperinsulinemic
      euglycemic clamp of 120 minutes duration is started. This implies intravenous infusion of
      insulin and glucose for 120 minutes in order to determine insulin sensitivity for glucose
      uptake and metabolism of glucose. The clamp is started with a bolus injection of insulin (9.0
      mU/kg) followed by a constant infusion (1.42 mU/kg/min). Simultaneously glucose infusion rate
      will be adjusted so that euglycemia is maintained. Immediately before, after 30 minutes and
      after 120 minutes of insulin infusion a muscle biopsy is taken from the vastus lateralis
      muscle in both legs (a total of 6 biopsies). Blood samples from both femoral veins and one
      femoral artery are taken before (at 12:00 p.m., 12:30 p.m., 1:00 p.m., 1:30 p.m. and 2:00
      p.m.) and during (at 2:15 p.m., 2:30 p.m., 2:45 p.m., 3:00 p.m., 3:15 p.m., 3:30 p.m., 3:45
      p.m. and 4:00 p.m.) the hyperinsulinemic euglycemic clamp. Simultaneously blood flow is
      measured in both femoral arteries with use of Doppler technique. Determination of
      arteriovenous difference (AV difference) by simultaneous measurement of blood flow enables us
      to calculate glucose uptake and uptake/release of relevant substances (proteins, peptides and
      metabolites etc.). Indirect calorimetry for determination of whole body metabolism is
      measured concomitantly, starting 2 hours after conclusion of exercise. The experimental part
      of trial B is concluded at 4:00 p.m. The study subjects receive food and drink and are
      observed for one hour before they may leave the research laboratory.

      Muscle biopsies and blood samples from trial A and B are stored in a locked -80ºC freezer.
      Muscle samples and blood samples will subsequently be used for miscellaneous analyses
      described under background.

      The trials (A and B) will be carried out in a randomized order and will be separated by a
      minimum of 14 days.
    

Intervention name(s): Exercise, insulin infusion
Intervention type(s): Other
Intervention description(s): Trial A: Acute one-legged exercise Trial B: Insulin infusion 4 hours after one-legged exercise
Intervention MeSH terms: Insulin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Lean control subjects and obese insulin resistant subjects undergo two different trials (trial A and B). Trial A aims to investigate the effect of acute exercise and 2 hours recovery. Trial B aims to investigate insulin sensitivity for glucose uptake in recovery from exercise.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Exercise; Insulin Resistance; Type 2 Diabetes; Glucose Uptake; Insulin Sensitivity