THE ROLE OF CNS INSULIN AS A MODULATOR OF DIABETIC COMPLICATIONS

糖尿病的特点是绝对或相对胰岛素 不足 这一缺陷引发了一系列事件 这导致糖尿病的主要特征：多食， 多饮多尿。 食欲增加，口渴和小便 生产已被归因于生理反应的营养 （葡萄糖）和水分流失。 然而，最近的研究表明， 中枢神经系统（CNS）剥夺以及外周神经系统 剥夺是重要的调解表达的一些 糖尿病的特点。 现在普遍认为胰岛素 确实能接触到B雨，大脑有胰岛素受体。 事实上，将胰岛素输注到脑室内（IVC）中， 被证明可以减少食欲和体重增加。 那么可以想象 外周胰岛素不足会导致中枢神经系统胰岛素不足， 慢性中枢神经系统功能不全可能导致特定的功能障碍， 中央自主控制机制，从而发挥重要作用 在继发性和长期内脏行为并发症中， 慢性糖尿病 这些并发症中最重要的是 心血管变化、胃肠道紊乱和代谢紊乱 改变，特别是葡萄糖和脂肪代谢。 在此提出的 在这项研究中，我们将研究中枢神经系统胰岛素状态的影响， 和糖尿病动物：（1）心血管调节和性能，（2） 摄食行为，（3）胃肠道分泌和运动，（4）肝脏 白色脂肪中的葡萄糖产生和（5）脂蛋白脂酶活性 组织. 外周激素、血浆代谢物和CNS神经肽， 生物胺水平将在所有实验中定量 条件 我们还将描述中枢神经系统的协调部位， 这些回应。 最后，内脏内分泌反应模式介导 将检查延髓中的孤束核（NTS）， 与由喙部CNS调节位点介导的反应模式相比， 就像下丘脑。 这些关于中枢胰岛素在糖尿病中作用的研究， 而正常的动物将揭示参与协调的机制 营养平衡的神经、内分泌和行为决定因素。 此外，这项研究将用于培训少数民族学生， 研究和调查技术。 因为这个节目有很多 不同程度的实验严谨性，它将是优秀的， 本科生和研究生的发展。

Diabetes in characterized by an absolute or relative insulin insufficiency. This deficiency sets in motion and a sequence of events that leads to tahe major features characteristic of diabetes; polyphagia, polydipsia and polyuria. The increased appetite, thirst and urine production have been attributed to the physiologic response to nutrient (glucose) and water loss. However, more recent studies have demonstrated that central nervous system (CNS) deprivation as well as peripheral deprivation is significant in mediating the expression of some of the characteristics of diabetes. it is now generally accepted that insulin does gain access to the b rain and that the brain has insulin receptors. Indeed the infusion of insulin into the intracerebroventricles (IVC) has been shown to decrease appetite and weight gain. It is then conceivable that a peripheral insulin insufficiency will result in a CNS insufficiency, and that chronic CNS insufficiency may lead to specific dysfunctions in central autonomic control mechanisms and thereby play a consequential role in the secondary and long term viscerobehavioral complications found in chronic diabetes. The most significant of these complications are cardiovascular changes, gastrointestinal disturbances and metabolic alterations, especially of glucose and fat metabolism. In this proposed study we will investigate the effect of the CNS insulin status in normal and diabetic animals on: (1) cardiovascular regulation and performance, (2) feeding behavior, (3) gastrointestinal secretion and motility, (4) hepatic glucose production and (5) lipoprotein lipase activity in white adipose tissue. Peripheral hormones, plasma metabolite and CNS neuropeptide and biogenic amine levels will be quantitated in all of the experimental conditions. We will also characterize the CNS site of the coordination of these responses. Finally, visceroendocrine response patterns mediated by the nucleus of the solitary tract (NTS) in the medulla will be examined and compared to response patterns mediated by rostral CNS regulatory sites such as the hypothalamus. These studies on the role of CNS insulin in diabetic and normal animals will shed light on mechanisms involved in coordinating neural, endocrine and behavioral determinants of nutrient homeostasis. Additionally, this study will be utilized to train minority students in research and investigative techniques. Because this program has many different levels of experimental rigor, it will be excellent in the development of both undergraduate and graduate students.