Insulin Resistance, Metabolic Disease, Mitochondrial Metabolism, Overweight and Obesity, Sedentary Lifestyle
Conditions
Brief summary
Our objective in this study is to identify the extent to which insulin drives the accumulation of lipids in skeletal muscle of humans. We will test the hypothesis that 4-hours of mild hyperinsulinemia will result in significant muscle lipid accumulation and that such effects will be similar in lean and overweight/obese humans.
Interventions
Participants will be administered a constant-rate insulin infusion (to induce mild hyperinsulinemia), with an infusion of dextrose to maintain blood glucose concentration (to maintain euglycemia).
Sponsors
Study design
Intervention model description
Participants will be asked to complete 1 screening visit to determine eligibility. If participants remain eligible, they will be asked to complete 1 metabolic study visit.
Eligibility
Inclusion criteria
* Age 30-55 years * Body mass index (BMI) 18-45 kg/m2 * Sedentary (\<1 hour of planned exercise per week)
Exclusion criteria
* Regular exercise (\>1 hour of planned exercise per week) * Smoking, tobacco or nicotine use within the last 1-year * Fasting glucose \>126mg/dL * Hypertension (systolic pressure \>140 mmHg or diastolic pressure \>90 mmHg) * Chronic metabolic or cardiovascular health conditions * Pregnant, nursing, irregular menses or post-menopausal * Lidocaine allergy * Certain medications * Diminished capacity for consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in skeletal muscle lipid content during hyperinsulinemia compared with basal resting conditions | Muscle samples will be collected in basal and hyperinsulinemic conditions separated by ~4.5 hours during the metabolic study visit | Liquid chromatography tandem mass spectrometry (targeted lipidomics) will be used to assess species-level changes in skeletal muscle lipid content in biopsy samples collected before and after the insulin infusion to induce mild hyperinsulinemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in skeletal muscle mitochondrial oxidative capacity during hyperinsulinemia compared with basal resting conditions | Muscle samples will be collected in basal and hyperinsulinemic conditions separated by ~4.5 hours during the metabolic study visit | High-resolution respirometry will be used to assess changes in skeletal muscle mitochondrial oxidative capacity in biopsy samples collected before and after the insulin infusion to induce mild hyperinsulinemia. |
Countries
United States