Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle

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

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: Intralipid, 20% Intravenous Emulsion; Dietary supplement: MitoQ; Drug: Salbutamol

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • August Krogh Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lipid infusion + MitoQ; Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion	Drug: Intralipid, 20% Intravenous Emulsion; Lipid infusion; Dietary supplement: MitoQ; Oral administration of MitoQ capsules; Other Names: Mitoquinone mesylate; Mitoquinone; MitoQ10
Placebo Comparator: Lipid infusion + placebo; Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by placebo administration and intravenous lipid infusion	Drug: Intralipid, 20% Intravenous Emulsion; Lipid infusion
No Intervention: Control; Subjects undergo a hyperinsulinemic isoglycemic clamp
Other: Lipid infusion + beta2-agonist; Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol	Drug: Intralipid, 20% Intravenous Emulsion; Lipid infusion; Drug: Salbutamol; Beta2-agonist infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	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)	Baseline

Collaborators and Investigators

• Sponsor: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Micronutrients; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Pharmaceutical Solutions; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Albuterol; Soybean oil, phospholipid emulsion; Ubiquinone
• Other Study ID Numbers: mtROS-IR

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