Biessels G J, Stevens E J, Mahmood S J, Gispen W H, Tomlinson D R
William Harvey Research Institute, Department of Pharmacology, Queen Mary and Westfield College, London, UK.
J Neurol Sci. 1996 Sep 1;140(1-2):12-20. doi: 10.1016/0022-510x(96)00080-9.
Decreased nerve blood flow may be a pathogenetic factor in diabetic neuropathy. Previously it was shown that insulin treatment, commenced at the onset of streptozotocin-diabetes, prevents the development of a nerve blood flow deficit in the diabetic rat. The present study sought to determine the effect of short-term (one month) and acute (one hour) insulin reversal treatment on nerve blood flow deficits in streptozotocin-diabetes. Sciatic nerve blood flow was assessed using laser Doppler flowmetry. Treatment was initiated after one month of diabetes. One month of reversal insulin treatment ameliorated nerve laser Doppler flux (NDF) deficits; in untreated diabetic rats NDF was 51% of that in control animals (P < 0.01), in insulin-treated diabetic rats NDF was 85% of control values (P < 0.01 vs. untreated diabetic, P < 0.05 vs. control). In association with blood flow increases, we found a significant amelioration of motor (P < 0.05 vs. untreated diabetic) and sensory (P < 0.01 vs. untreated diabetic) nerve conduction velocities but not of exaggerated resistance to hypoxic conduction block. Insulin partially reversed hyperglycaemia and sciatic nerve polyol and sugar levels. In a second experiment, in rats with one month of diabetes, acute infusion of insulin led to a 47% (P < 0.001 vs. pre-insulin values) reduction of plasma glucose. This fall in plasma glucose was accompanied by a 38% (P < 0.05 vs. pre-insulin values) increase in NDF. Sensory nerve conduction velocity was marginally increased (6%, P < 0.05 vs. pre-insulin values) after insulin infusion, but motor conduction velocity was not. The data indicate that insulin can partially reverse deficits in nerve blood flow and conduction in diabetic rats.
神经血流减少可能是糖尿病性神经病变的一个致病因素。此前有研究表明,在链脲佐菌素诱导糖尿病发病时开始胰岛素治疗,可预防糖尿病大鼠出现神经血流不足。本研究旨在确定短期(1个月)和急性(1小时)胰岛素逆转治疗对链脲佐菌素诱导糖尿病大鼠神经血流不足的影响。使用激光多普勒血流仪评估坐骨神经血流。糖尿病1个月后开始治疗。1个月的胰岛素逆转治疗改善了神经激光多普勒通量(NDF)不足;未治疗的糖尿病大鼠NDF为对照动物的51%(P<0.01),胰岛素治疗的糖尿病大鼠NDF为对照值的85%(与未治疗糖尿病大鼠相比P<0.01,与对照相比P<0.05)。随着血流增加,我们发现运动神经传导速度(与未治疗糖尿病大鼠相比P<0.05)和感觉神经传导速度(与未治疗糖尿病大鼠相比P<0.01)有显著改善,但对缺氧传导阻滞的过度抵抗没有改善。胰岛素部分逆转了高血糖以及坐骨神经多元醇和糖水平。在第二个实验中,对糖尿病1个月的大鼠进行急性胰岛素输注,导致血浆葡萄糖降低47%(与胰岛素输注前值相比P<0.001)。血浆葡萄糖的这种下降伴随着NDF增加38%(与胰岛素输注前值相比P<0.05)。胰岛素输注后感觉神经传导速度略有增加(6%,与胰岛素输注前值相比P<0.05),但运动传导速度没有增加。数据表明胰岛素可部分逆转糖尿病大鼠的神经血流和传导不足。