Exercise and Insulin Signaling in Human Skeletal Muscle

Study Overview
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Brief Summary
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Obesity is associated with a decrease in skeletal muscle insulin sensitivity. Aerobic exercise can increase insulin sensitivity in the few hours following exercise, however the cellular mechanisms are not completely understood. The current project is to investigate mechanisms of exercise improvements to skeletal muscle insulin sensitivity.

Detailed Description
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Study Overview: We are investigating the mechanisms by which exercise improves the response of skeletal muscle to insulin in lean and obese adults. Participants will complete 4 study visits consisting of: 1) screening visit, 2) maximal exercise test visit, and then a randomized order of 3) a resting metabolic study visit, and 4) an exercise metabolic study visit. Metabolic study visits for resting and exercise conditions will be identical, other than remaining sedentary or performing exercise. Skeletal muscle biopsy samples will be collected during resting, immediately post-exercise and during insulin stimulated conditions.

Official Title
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Exercise and Insulin Signaling in Human Skeletal Muscle

Conditions
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Insulin Sensitivity, Obesity, Sedentary Lifestyle

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or Females Aged 18-45 years Normal weight (body mass index [BMI] 18-26 kg/m2) or obese (BMI 30-46 kg/m2) Sedentary (< 1 hour of planned physical activity per week for ≥ 6 months) Weight stable (< 2 kg change in body mass for ≥ 6 months) Non-smokers (no tobacco or nicotine use for ≥ 1 year) Exclusion Criteria: Hypertension (systolic blood pressure >140 mmHg, diastolic blood pressure > 90mmHg) Chronic health condition including diabetes, cardiovascular disease, treated hypertension, cancer, anemia, uncontrolled hyper- or hypothyroidism. Pregnant, nursing, irregular menses or post-menopausal (if female) Hyperglycemia (fasting glucose >126 mg/dl) Hypercholesterolemia (fasting LDL>140mg/dl) Hemoglobin < 13.0 g/dl (males), < 11.5 g/dl (females) Compromised renal function (outside 135-145 mmol/L sodium, 3.5-5.1 mmol/L potassium) Lidocaine allergy Medications including β-blockers, angiotensin converting enzyme inhibitors, insulin, thiazolidinediones, metformin, sulfonylureas, chronic non-steroidal anti-inflammatory use, anti-coagulant (e.g. warfarin), current antibiotics, opiates, monoamine oxidase inhibitors, benzodiazepines, or others that may impact the study outcomes Any physical limitation that prevents a participant from safely completing the exercise test Due to the risks associated with the current protocol, individuals with a diminished capacity to consent will be excluded. Similarly, due to the need for constant, accurate participant monitoring during metabolic study activities, participants will need to clearly understand verbal and written English. Participants who cannot clearly understand verbal and written English will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Metabolic Study Day<br>Participants will perform a single bout of moderate intensity exercise on a cycle ergometer for 60 minutes. A total of 3 muscle biopsies will be collected throughout the study day. Insulin sensitivity will be measured using a hyperinsulinemic-euglycemic clamp with glucose tracers. | Behavioral: Exercise<br>* Participants will perform 2 metabolic study days of either resting or acute bout of cycling exercise in a randomized cross-over design.<br>|
| No Intervention: Resting Metabolic Study Day<br>Participants will rest quietly in bed for 60 minutes and resting energy metabolism will be measured with a ventilated hood. A total of 3 muscle biopsies will be collected throughout the study day. Insulin sensitivity will be measured using a hyperinsulinemic-euglycemic clamp with glucose tracers. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle insulin sensitivity | Skeletal muscle insulin sensitivity will be measured by hyperinsulinemic-euglycemic clamp. | 2 hours following rest or exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise