title: Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.
abstract: The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.
authors.affiliation: Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Dotzert
authors.affiliation: Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Murray
authors.affiliation: Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: McDonald
authors.affiliation: Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: T Dylan
authors.initials: TD
authors.lastname: Olver
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Velenosi
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Anzel
authors.initials: A
authors.lastname: Hennop
authors.affiliation: Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: Earl G
authors.initials: EG
authors.lastname: Noble
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.|Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Brad L
authors.initials: BL
authors.lastname: Urquhart
authors.affiliation: Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: C W James
authors.initials: CW
authors.lastname: Melling
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D015309:Glucose Clamp Technique; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D057185:Sedentary Behavior; D013311:Streptozocin
chemical_list: D005227:Fatty Acids; D013311:Streptozocin