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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 (·-) overproductionand 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, NOSand 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.
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Contributor : Laurent Jonchère <>
Submitted on : Wednesday, June 3, 2015 - 11:11:58 AM
Last modification on : Monday, February 15, 2021 - 10:38:02 AM



Ludivine Malardé, Amélie Rébillard, S Le Douairon-Lahaye, S Vincent, Ms Zguira, et al.. Superoxide production pathways in aortas of diabetic rats: beneficial effects of insulin therapy and endurance training.. Molecular and Cellular Biochemistry, Springer Verlag, 2014, 389 (1-2), pp.113-118. ⟨10.1007/s11010-013-1932-z⟩. ⟨hal-01159343⟩



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