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The purpose of the study is to evaluate the link between insulin resistance and alterations in skeletal muscle mitochondrial redox homeostasis
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lipid infusion + MitoQ | Experimental | Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion |
|
| Lipid infusion + placebo | Placebo Comparator | Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by placebo administration and intravenous lipid infusion |
|
| Control | No Intervention | Subjects undergo a hyperinsulinemic isoglycemic clamp | |
| Lipid infusion + beta2-agonist | Other | Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intralipid, 20% Intravenous Emulsion | Drug | Lipid infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Whole body Insulin sensitivity | Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method | 5 hours after lipid infusion |
| Skeletal muscle insulin sensitivity | 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 | 5 hours after lipid infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Mitochondrial respiration | Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry | Baseline |
| Mitochondrial reactive oxygen species | Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiorespiratory fitness | Pulmonary maximal oxygen uptake (VO2max) is determined during an incremental exercise test to exhaustion | Baseline |
| Body composition | Fat free mass and fat mass are determined by dual-energy X-ray absorptiometry (DXA) |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| August Krogh Building | Copenhagen | Denmark |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C545823 | soybean oil, phospholipid emulsion |
| C429014 | mitoquinone |
| D000420 | Albuterol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| MitoQ | Dietary Supplement | Oral administration of MitoQ capsules |
|
|
| Salbutamol | Drug | Beta2-agonist infusion |
|
| Baseline |
| Mitochondrial oxidative stress | Peroxiredoxin3 dimer/monomer ratio is determined in skeletal muscle biopsies | Before (baseline) as well as 3 and 5 hours after lipid infusion |
| Muscle redox status | GSH/GSSG ratio is determined in skeletal muscle biopsies | Before (baseline) as well as 3 and 5 hours after lipid infusion |
| Insulin signalling | Phosphorylation status of proteins modulating insulin action is determined in skeletal muscle biopsies | Before (baseline) as well as 3 and 5 hours after lipid infusion |
| Baseline |
| D000588 |
| Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |