Insulin and Muscle Fat Metabolism

Study Overview
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Brief Summary
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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.

Official Title
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Insulin and Muscle Fat Metabolism

Conditions
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Overweight and Obesity, Insulin Resistance, Metabolic Disease, Mitochondrial Metabolism, Sedentary Lifestyle

Intervention / Treatment
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* Other: Hyperinsulinemic-euglycemic Clamp


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metabolic Study Visit<br>Participants will complete a study visit for metabolic phenotyping and determination of the impact of hyperinsulinemia on outcomes of interest. | Other: Hyperinsulinemic-euglycemic Clamp<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in skeletal muscle lipid content during hyperinsulinemia compared with basal resting conditions | 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. | Muscle samples will be collected in basal and hyperinsulinemic conditions separated by  4.5 hours during the metabolic study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in skeletal muscle mitochondrial oxidative capacity during hyperinsulinemia compared with basal resting conditions | 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. | Muscle samples will be collected in basal and hyperinsulinemic conditions separated by  4.5 hours during the metabolic study visit |