Insulin Resistance
Conditions
Brief summary
The purpose of the study is to evaluate the link between insulin resistance and alterations in skeletal muscle mitochondrial redox homeostasis
Interventions
Lipid infusion
DIETARY_SUPPLEMENTMitoQ
Oral administration of MitoQ capsules
DRUGSalbutamol
Beta2-agonist infusion
Sponsors
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) ≥25 and \<40 kg/m2 * Fasting plasma glucose ≥ 5.6 mmol/L or HbA1c ≥ 5.7% * HOMA2-IR \> 1.4 * VO2max \<45 ml/kg/min
Exclusion criteria
* Treatment with \>2 antidiabetic medications * Insulin usage * Chronic disease deemed by the study responsible medical doctor to interfere with any part of the study * Chronic use of prescription medicine deemed by the study responsible medical doctor to interfere with any part of the study * Smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal muscle insulin sensitivity | 5 hours after lipid infusion | Insulin-dependent skeletal muscle glucose uptake is determined by hyperinsulinemic isoglycemic clamp method integrated with measurements of femoral artery blood flow and arteriovenous difference of glucose |
| Whole body Insulin sensitivity | 5 hours after lipid infusion | Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mitochondrial reactive oxygen species | Baseline | Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry |
| Muscle redox status | Before (baseline) as well as 3 and 5 hours after lipid infusion | GSH/GSSG ratio is determined in skeletal muscle biopsies |
| Insulin signalling | Before (baseline) as well as 3 and 5 hours after lipid infusion | Phosphorylation status of proteins modulating insulin action is determined in skeletal muscle biopsies |
| Mitochondrial oxidative stress | Before (baseline) as well as 3 and 5 hours after lipid infusion | Peroxiredoxin3 dimer/monomer ratio is determined in skeletal muscle biopsies |
| Mitochondrial respiration | Baseline | Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiorespiratory fitness | Baseline | Pulmonary maximal oxygen uptake (VO2max) is determined during an incremental exercise test to exhaustion |
| Body composition | Baseline | Fat free mass and fat mass are determined by dual-energy X-ray absorptiometry (DXA) |
Countries
Denmark
Outcome results
None listed