DISORDER OF MET ENCEPHALIN LEVELS IN DIABETES

糖尿病的并发症很多，表现为广泛的 包括反应异常在内的一系列病理情况 对痛苦的刺激。内源性阿片肽在中介中的作用 在动物和人类中的抗伤害作用的研究已经被记录在案。我们 发现链脲佐菌素(STZ)诱导的大鼠糖尿病 在开发出的热板潜伏期测试中显著增加 在诱发糖尿病后的6-7周内逐渐增加。这 镇痛反应与几倍的游离增加有关 血浆和不同脑区的甲硫氨酸脑啡肽(ME)。的目的 这些研究是为了确定调节细胞周期的神经化学基础。 糖尿病患者内源性代谢能水平的变化我们假设最高的 游离代谢能水平是释放的异常激活的结果 从较大的矿藏(前体)中处理ME和/或减少其 周转率。为了检验这一假设，我们将确定：(1)是否 大鼠血浆、脊髓和脑组织中高水平的游离ME 糖尿病是由于ME释放增加和/或其减少所致 降解性，(2)如果糖尿病患者的高循环血糖水平 在增加代谢能水平方面起作用，(3)是否增加 游离代谢能水平受另一种内源性激素的间接调节 糖尿病引起的神经递质(即DA)，(4)如果糖尿病 改变游离ME和/或其直接前体的动力学(神秘 表格)，(5)是否用慢性胰岛素控制糖尿病状态 管理部门防止、改善或逆转 代谢能水平和分布与非糖尿病对照组相似 老鼠。 除了检验这一假设外，我们还计划确定 这种变化在诱导后发展的时间进程 糖尿病以及纠正这种疾病的胰岛素治疗计划 有问题。这些研究应该提供对以下因素的洞察 调节糖尿病患者的ME水平并间接应用止痛药 作为与此相关的病理生理状态之一的反应 疾病。如果糖尿病患者的状态发生改变 ME的释放和/或流动率，这些结果可能会提供 药物治疗或药物相互作用的合理基础 糖尿病患者的抗伤害感受系统。

Complications of diabetes Mellitus are numerous and manifested by a wide range of pathological conditions including abnormalities in the response to painful stimuli. The role of endogenous opioid peptides in mediation of antinociceptive effect in animal and human has been documented. We have found that streptozotocin (STZ)-induced diabetes in rats resulted in a significant increase in the hot plate latency test which developed gradually over 6-7 weeks period post induction of diabetes. this analgesic response was associated with several-folds increase of free Met-enkephalin (ME) in plasma and various brain regions. The object of these studies is to determine the neurochemical basis that regulate the level of the endogenous ME in diabetes. We hypothesize that the high level of free ME is a result of an abnormal activation of the releasing process of ME from the larger pool (precursor) and/or decrease in its turn over rate. To test this hypothesis, we will determine: (1) Whether the high level of free ME in plasma, spinal cord and brain regions in diabetes is due to enhanced ME release and/or decrease in its degradation, (2) if the high circulating level of glucose in diabetes plays a role in increasing the level of ME, (3) whether the increase in free ME level is modulated indirectly by another endogenous neurotransmitter (i.e., DA) as a result of diabetes, (4) if diabetes alters the kinetic of free ME and/or its immediate precursor (cryptic form), (5) whether controlling the diabetic state with chronic insulin administration prevents, ameliorates or reverse such alteration in the level, and distribution of ME similar to that of the non-diabetes control rat. In addition to testing this hypothesis, we also plan to determine the time course for the development of such changes after the induction of diabetes as well as the schedule of insulin treatment that correct such problems. These studies should provide insight into the factors that regulate the level of ME in diabetes and indirectly, the analgesic response as one of the pathophysiological condition associated with this disease. Should the diabetic state produce an alteration in the releasing and/or turnover rate of ME, these results might provide a rational basis for drug treatment or drug interaction involving the antinociceptive system of diabetic patients.