title: Superoxide production pathways in aortas of diabetic rats: beneficial effects of insulin therapy and endurance training.
abstract: Superoxide (O 2 (·-) ) overproduction, by decreasing the nitric oxide ((·)NO) bioavailability, contributes to vascular complications in type 1 diabetes. In this disease, the vascular O 2 (·-) can be produced by the NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO). This study aimed to determine the contribution of each enzymatic pathway in hyperglycemia-induced O 2 (·-) overproduction, and the effects of an endurance training program and insulin therapy, associated or not, on the O 2 (·-) production (amount and related enzymes) in diabetic rats. Forty male Wistar rats were divided into diabetic (D), diabetic treated with insulin (D-Ins), diabetic trained (D-Tr), or diabetic insulin-treated and trained (D-Ins + Tr) groups. An additional healthy group was used as control. Insulin therapy (Glargine Lantus, Sanofi) and endurance training (treadmill run: 60 min/day, 25 m/min, 5 days/week) started 1 week after diabetes induction by streptozotocin (45 mg/kg), and lasted for 8 weeks. At the end of the protocol, the O 2 (·-) production in aorta rings was evaluated by histochemical analyses (DHE staining). Each production pathway was studied by inhibiting NOX (apocynin), NOS (L-Name), or XO (allopurinol) before DHE staining. Diabetic rats exhibited hyperglycemia-induced O 2 (·-) overproduction, resulting from NOX, NOS, and XO activation. Insulin therapy and endurance training, associated or not, decreased efficiently and similarly the O 2 (·-) overproduction. Insulin therapy reduced the hyperglycemia and decreased the three enzymatic pathways implicated in the O 2 (·-) production. Endurance training decreased directly the NOS and XO activity. While both therapeutic strategies activated different pathways, their association did not reduce the O 2 (·-) overproduction more significantly.
authors.affiliation: Laboratoire M2S, Université Rennes 2 - ENS Cachan, Avenue Robert Schuman, 35170, Bruz, France, ludivine.malarde@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Malardé
authors.forename: A
authors.initials: A
authors.lastname: Rebillard
authors.forename: S
authors.initials: S
authors.lastname: Le Douairon-Lahaye
authors.forename: S
authors.initials: S
authors.lastname: Vincent
authors.forename: M S
authors.initials: MS
authors.lastname: Zguira
authors.forename: S
authors.initials: S
authors.lastname: Lemoine-Morel
authors.forename: A
authors.initials: A
authors.lastname: Gratas-Delamarche
authors.forename: C
authors.initials: C
authors.lastname: Groussard
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen; D010807:Physical Endurance / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007328:Insulin; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen