How is Glycogen Supercompensation Regulated in Human Skeletal Muscle (Supercomp)

Regulation of Glycogen Supercompensation in Human Skeletal Muscle

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.

Study Overview

• Status: Completed
• Conditions: Insulin Sensitivity; Glycogen Depletion
• Intervention / Treatment: Other: Glycogen Supercompensation

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2100
      • Department of Nutrition, Exercise and Sports

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male
• BMI between BMI 20-25 kg/m2
• healthy and not using medication
• not smoking
• habitual physical activity level of 2 - 6 hours pr. week
• no incidence of diabetes, cardiovascular disease or other metabolic diseases in close family

Exclusion Criteria:

• female
• BMI below 20 and above 25 kg/m2
• using medication
• smoking
• habitual physical activity level below 2 h pr. week or above 6 hours pr. week
• incidence of diabetes, cardiovascular disease or metabolic disease in close family

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin action in skeletal muscle	Insulin action in skeletal muscle was investigated during hyperinsulinemic euglycemic conditions by combining AV-difference with blood flow measurements.	1 week

Collaborators and Investigators

• Sponsor: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2013
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): December 31, 2014

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: March 1, 2018
• First Posted (Actual): March 8, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: Supercomp

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No