Effects of chronic exercise on endothelial dysfunction and insulin signaling of cutaneous microvascular in streptozotocin-induced diabetic rats

Abstract

Background: Abnormalities of the modulatory roles played by the endothelium and/or smooth muscle may be critical and initiating factors in the development of diabetic vascular disease. Decreased phosphatidylinositol 3-kinase (PI3-K)/Akt pathway activity and impaired nitric oxide production through this pathway may play pivotal roles in the diabetes-induced vascular dysfunction. Several findings have demonstrated that exercise training has therapeutic and protective effects in type 1 diabetes and could correct endothelial dysfunction. The molecular mechanisms, however, are only partially understood.

Method: Male Wistar rats (220+/-10 g, N=60) were made diabetic by streptozotocin (60 mg/kg, subcutaneously). After 1 week of diabetes induction, animals were submitted to exercise training for 10 weeks on a treadmill. To characterize cutaneous microvascular responses by laser Doppler flowmetery, animals were deeply anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and placed on a heating pad. A rectal thermometer was inserted and body temperature was maintained at 37+/-0.5 degrees C. A tracheotomy was performed to minimize respiratory difficulties. Systemic arterial blood pressure and heart rate were measured by using a tail-cuff during assessment of cutaneous blood flow.

Results: (i) Acetylcholine-induced cutaneous perfusion were increased significantly by training in the diabetic groups; (ii) Cutaneous microvascular responses to sodium nitroprusside did not alter in control and diabetic animals by training; and (iii) Local microinjection of insulin increased cutaneous blood flow in trained diabetic and trained control rats compared with age-matched sedentary diabetic and sedentary control normal rats. The administration of wortmannin (PI3K inhibitor) and N-nitro-L-arginine ( nitric oxide synthase inhibitor) before insulin, however, attenuated the increase in cutaneous blood flow in trained diabetic and normal rats.

Conclusions: Chronic exercise improved endothelium-dependent dilatation and potentiated insulin vascular function, possibly by PI3-kinase pathway in diabetic rats.