Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle

Not Applicable

Completed

• Conditions: Insulin Resistance
• Interventions: Drug: Intralipid, 20% Intravenous Emulsion; Dietary Supplement: MitoQ; Drug: Salbutamol

• Registration Number: NCT04558190
• Lead Sponsor: University of Copenhagen

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-02
• Study First Submitted: 2020-09-02
• Study First Submitted QC: 2020-09-15
• Study First Posted: 2020-09-22
• Primary Completion: 2021-11-01
• Study Completion: 2021-11-01
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-01
• Last Update Posted: 2021-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Lipid infusion + placebo	Intralipid, 20% Intravenous Emulsion	Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by placebo administration and intravenous lipid infusion
Lipid infusion + MitoQ	MitoQ	Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion
Lipid infusion + MitoQ	Intralipid, 20% Intravenous Emulsion	Subjects undergo a hyperinsulinemic isoglycemic clamp preceded by MitoQ administration and intravenous lipid infusion
Lipid infusion + beta2-agonist	Intralipid, 20% Intravenous Emulsion	Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol
Lipid infusion + beta2-agonist	Salbutamol	Subjects undergo a hyperinsulinemic isoglycemic clamp with intravenous infusion of lipid and salbutamol

Primary Outcome Measures

Name	Time	Method
Whole body Insulin sensitivity	5 hours after lipid infusion	Whole body insulin sensitivity is determined by hyperinsulinemic isoglycemic clamp method
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

Secondary Outcome Measures

Name	Time	Method
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 respiration	Baseline	Mitochondrial O2 flux is determined in skeletal muscle biopsies by high-resolution fluorespirometry
Mitochondrial reactive oxygen species	Baseline	Mitochondrial H2O2 emission rate is determined in skeletal muscle biopsies by high-resolution fluorespirometry
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
Muscle redox status	Before (baseline) as well as 3 and 5 hours after lipid infusion	GSH/GSSG ratio is determined in skeletal muscle biopsies

Trial Locations

Locations (1)

August Krogh Building; 🇩🇰 Copenhagen, Denmark