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

Inclusion criteria

• Age 30-65 years
• Men and women
• Body mass index (BMI) between 25 and 45 kg/m2
• Sedentary (1 day or less per week of structured exercise)
• Type 2 diabetes mellitus determined by self-report or by a fasting glucose >126mg/dl
• Weight stable (± 2 kg) for prior 3 months
• Willing to commit to the schedule of assessment visits, including the exercise intervention

Exclusion criteria

• Currently taking insulin, injectable incretin mimetics and thiazolidinediones
• Taking more than two glucose-lowering medications
• Resting blood pressure ≥ 160/100 mm Hg
• Triglycerides ≥ 500 mg/dL
• 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
• Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
• Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training
• Pulse check ("Allen test") indicates participant has poor blood flow in the hands
• Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma)
• Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year
• Use of drugs known to affect energy metabolism or body weight: including, but not limited to orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
• Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
• 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.
• New onset (<3 months on a stable regime) hormone replacement therapy
• Current use of beta-adrenergic blocking agents
• Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
• Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal)
• Abnormal blood count/anemia, blood transfusion or blood donation within the last 2 months
• Current smokers (smoking within the past 3 months prior to screening visit, including any/all tobacco products)
• Current drug or alcohol abuse/dependence
• Metal implants (pace-maker, aneurysm clips) based on investigator's judgment at screening
• Not physically capable of performing the exercise required of the study protocols
• Plans to be away >2 weeks in the next 3 months
• 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.
• Unable to tolerate MRI or claustrophobia.
• Nickel allergy
• Lidocaine allergy
• Unable or unwilling to communicate with staff or to provide written informed consent