Superoxide production pathways in aortas of diabetic rats: beneficial effects of insulin therapy and endurance training

• Published in: Molecular and cellular biochemistry 2014-04, Vol.389 (1-2), p.113-118
• Main Authors: Malardé, L., Rebillard, A., Le Douairon-Lahaye, S., Vincent, S., Zguira, M. S., Lemoine-Morel, S., Gratas-Delamarche, A., Groussard, C.
• Format: Article
• Language: English
• Subjects: Animals; Aorta - metabolism; Bioavailability; Biochemistry; Biomedical and Life Sciences; Cardiology; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes therapy; Drug therapy; Exercise; Health aspects; Hyperglycemia; Hyperglycemia - metabolism; Insulin; Insulin - metabolism; Life Sciences; Male; Medical Biochemistry; Molybdenum compounds; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Oncology; Oxidases; Oxygen; Physical Endurance - physiology; Physical fitness; Rats; Rats, Wistar; Rodents; Signal Transduction - physiology; Streptozocin; Superoxide; Superoxides - metabolism; Training; Type 1 diabetes
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1932-z

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.