Heidarianpour Ali, Hajizadeh Sohrab, Khoshbaten Ali, Niaki Abbas Ghanbari, Bigdili Mohammad Reza, Pourkhalili Khalil
Department of Physiology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Eur J Cardiovasc Prev Rehabil. 2007 Dec;14(6):746-52. doi: 10.1097/HJR.0b013e32817ed02f.
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.
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.
(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.
Chronic exercise improved endothelium-dependent dilatation and potentiated insulin vascular function, possibly by PI3-kinase pathway in diabetic rats.
内皮细胞和/或平滑肌所起调节作用的异常可能是糖尿病血管疾病发生发展的关键起始因素。磷脂酰肌醇3激酶（PI3-K）/Akt信号通路活性降低以及通过该通路产生一氧化氮受损，可能在糖尿病诱导的血管功能障碍中起关键作用。多项研究结果表明，运动训练对1型糖尿病具有治疗和保护作用，并可纠正内皮功能障碍。然而，其分子机制仅得到部分理解。
雄性Wistar大鼠（220±10 g，n = 60）通过链脲佐菌素（60 mg/kg，皮下注射）诱导糖尿病。糖尿病诱导1周后，将动物置于跑步机上进行10周的运动训练。为通过激光多普勒血流仪表征皮肤微血管反应，通过腹腔注射戊巴比妥钠（60 mg/kg）使动物深度麻醉，并置于加热垫上。插入直肠温度计并将体温维持在37±0.5℃。进行气管切开术以尽量减少呼吸困难。在评估皮肤血流期间，使用尾套测量全身动脉血压和心率。
（i）糖尿病组中，训练使乙酰胆碱诱导的皮肤灌注显著增加；（ii）训练对对照组和糖尿病动物皮肤微血管对硝普钠的反应无影响；（iii）与年龄匹配的久坐糖尿病大鼠和久坐对照正常大鼠相比，局部注射胰岛素可增加训练的糖尿病大鼠和训练的对照大鼠的皮肤血流量。然而，在胰岛素注射前给予渥曼青霉素（PI3K抑制剂）和N-硝基-L-精氨酸（一氧化氮合酶抑制剂）可减弱训练的糖尿病大鼠和正常大鼠皮肤血流量的增加。
慢性运动可能通过PI3激酶途径改善糖尿病大鼠的内皮依赖性舒张并增强胰岛素血管功能。
