How is Glycogen Supercompensation Regulated in Human Skeletal Muscle
Condition: Glycogen Depletion; Insulin Sensitivity
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      Nine healthy, moderately fit male volunteers participated in the study. The subjects gave
      written informed consent after having been informed of any possible risk and discomfort
      associated with the study. The study was approved by the regional ethics committee in Denmark
      (Journal number: H-4-2013-071) and performed in accordance with the Declarations of Helsinki
      II.

      All subjects underwent 3 clinical investigations (day 1, day 2 and day 5) during a 5 day
      glycogen supercompensation regime. The subjects were asked to refrain from physical activity
      and to eat a controlled diet containing 60% carbohydrates (CHO) for 4 days prior to the
      initial experiments.

      Upon arrival at the laboratory on day 1, the subjects performed one-legged knee extensor
      exercise for 1 hour at 80% of PWL interspersed by 5 min bouts at 90% of PWL. This was
      followed by interval exercise until exhaustion containing 4 min bouts starting at 100% PWL
      followed by 1 min at 50% of PWL. Upon cessation of exercise the subjects showered and rested
      in the supine position for 4 hours. Then a 120 min hyperinsulinemic euglycemic clamp was
      initiated by a bolus insulin injection (9.0 mU/kg, Actrapid, Novo Nordisk, Denmark) followed
      by continuous insulin infusion (1.42 mU/kg/min insulin) reaching a level of plasma insulin
      around 100 µU/mL (n=9). At least 2 hours before the insulin clamp, catheters were placed in
      both femoral, one antecubital and one dorsal hand vein. A heat pad was placed around the
      lower part of the arm and hand in order to "arterialize" blood drawn from the hand vein.
      Substrate uptake/release across the legs was calculated by multiplying the arterial-venous
      (AV) difference in blood substrate concentration by femoral arterial blood flow (measured by
      ultrasound, Philips DICOM). Blood glucose levels were maintained at the euglycemic predefined
      target by continuously adjusting the glucose infusion rate (GIR) (20% glucose solution;
      Fresenius Kabi, Sweden). Concurrent measures of substrate AV differences and blood flow were
      performed every 20 min. Muscle biopsies from m. vastus lateralis were obtained under local
      anaesthesia (3-5 ml of Xylocaine, 20 mg/ml.) in the basal- and insulin-stimulated state (120
      min) by use of needle biopsy technique. Muscle specimen were frozen within 20 sec in liquid
      nitrogen and stored at -80°C for further analysis. A new incision was made for every biopsy
      and spaced 4-5 cm apart.

      This insulin clamp procedure in combination with basal and insulin stimulated muscle biopsies
      was repeated in the rested state (without prior exercise) on day 2 and day 5. The subjects
      arrived in the morning in the overnight fasted state at day 1, day 2 and day 5. During the 5
      day supercompensation regime the subjects were provided a predefined isocaloric diet
      containing 80% carbohydrates, 10% fat and 10% proteins. All food items were handle out to the
      subjects and compliance of the diet regime was ensured by survey.
    


Intervention name(s): Glycogen Supercompensation
Intervention type(s): Other
Intervention description(s): The subjects arrived in the morning in the overnight fasted state at day 1, day 2 and day 5. Upon arrival in the morning the subjects were given a meal corresponding to 5% of their daily energy intake (~600-800 kJ). During the 5 day supercompensation regime the subjects were provided a predefined isocaloric diet containing 80% carbohydrates, 10% fat and 10% proteins. All food items were handle out to the subjects and compliance of the diet regime was ensured by survey.
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Basic Science