Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes

Eligibility Criteria

• 1. Age 30-65 years
• 2. Men and women
• 3. Body mass index (BMI) between 25 and 45 kg/m2
• 4. Sedentary (1 day or less per week of structured exercise)
• 5. Type 2 diabetes mellitus determined by self-report or by a fasting glucose \>126mg/dl
• 6. Weight stable (± 2 kg) for prior 3 months
• 7. Willing to commit to the schedule of assessment visits, including the exercise intervention
• 1. Currently taking insulin, injectable incretin mimetics and thiazolidinediones
• 2. Taking more than two glucose-lowering medications
• 3. Resting blood pressure ≥ 160/100 mm Hg
• 4. Triglycerides ≥ 500 mg/dL
• 5. Any renal, cardiac, liver, lung, or neurological disease that in the opinion of the principal investigator would compromise participant safety or the participants' ability to complete the exercise training protocol
• 6. Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
• 7. Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training
• 8. Pulse check ("Allen test") indicates participant has poor blood flow in the hands
• 9. Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma)
• 10. Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year
• 11. Use of drugs known to affect energy metabolism or body weight: including, but not limited to orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
• 12. Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
• 13. Participant is currently taking anti-inflammatory medication or has had inflammatory medication within 1 week prior to screening (including over the counter formulations: e.g. Aleve, Motrin, Ibuprofen, Naproxen, low dose ASA.
• 14. New onset (\<3 months on a stable regime) hormone replacement therapy
• 15. Current use of beta-adrenergic blocking agents
• 16. Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
• 17. Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal)
• 18. Abnormal blood count/anemia, blood transfusion or blood donation within the last 2 months
• 19. Current smokers (smoking within the past 3 months prior to screening visit, including any/all tobacco products)
• 20. Current drug or alcohol abuse/dependence
• 21. Metal implants (pace-maker, aneurysm clips) based on investigator's judgment at screening
• 22. Not physically capable of performing the exercise required of the study protocols
• 23. Plans to be away \>2 weeks in the next 3 months
• 24. Unable to participate in Magnetic Resonance Imaging (MRI) assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on investigator's judgment at screening.
• 25. Unable to tolerate MRI or claustrophobia.
• 26. Nickel allergy
• 27. Lidocaine allergy
• 28. Unable or unwilling to communicate with staff or to provide written informed consent