Exercise and Insulin Signaling in Human Skeletal Muscle

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Sedentary Lifestyle; Insulin Sensitivity
• Intervention / Treatment: Behavioral: Exercise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Corvallis, Oregon, United States, 97331
      • Oregon State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Metabolic Study Day; 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; Participants will perform 2 metabolic study days of either resting or acute bout of cycling exercise in a randomized cross-over design.
No Intervention: Resting Metabolic Study Day; 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?

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

Collaborators and Investigators

• Sponsor: Oregon State University

Publications and helpful links

General Publications

• Newsom SA, Stierwalt HD, Ehrlicher SE, Robinson MM. Substrate-Specific Respiration of Isolated Skeletal Muscle Mitochondria after 1 h of Moderate Cycling in Sedentary Adults. Med Sci Sports Exerc. 2021 Jul 1;53(7):1375-1384. doi: 10.1249/MSS.0000000000002615.
• Stierwalt HD, Ehrlicher SE, Robinson MM, Newsom SA. Skeletal Muscle ACSL Isoforms Relate to Measures of Fat Metabolism in Humans. Med Sci Sports Exerc. 2021 Mar 1;53(3):624-632. doi: 10.1249/MSS.0000000000002487.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): June 28, 2018
• Study Completion (Actual): June 28, 2018

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 9, 2016

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 23, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: exercise
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 7605

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
• product manufactured in and exported from the U.S.: No