Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle

University of Copenhagen10 enrolled

Overview

The purpose of the study is to evaluate the link between insulin resistance and alterations in skeletal muscle mitochondrial redox homeostasis

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Insulin Resistance

Interventions

Intralipid, 20% Intravenous EmulsionDRUG

Lipid infusion

MitoQDIETARY_SUPPLEMENT

Oral administration of MitoQ capsules

SalbutamolDRUG

Beta2-agonist infusion

Eligibility

Sex: MALEMin age: 40 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

August Krogh Building

Copenhagen, Denmark

Outcomes

Primary Outcomes

Whole body Insulin sensitivity

Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method

Time frame: 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

Time frame: 5 hours after lipid infusion

Secondary Outcomes

Mitochondrial respiration

Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry

Time frame: Baseline

Mitochondrial reactive oxygen species

Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry

Time frame: Baseline

Mitochondrial oxidative stress

Peroxiredoxin3 dimer/monomer ratio is determined in skeletal muscle biopsies

Time frame: Before (baseline) as well as 3 and 5 hours after lipid infusion

Muscle redox status

GSH/GSSG ratio is determined in skeletal muscle biopsies

Time frame: 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

Time frame: Before (baseline) as well as 3 and 5 hours after lipid infusion

Data from ClinicalTrials.gov

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