BEHAVIORAL PHYSIOLOGY OF BODY WEIGHT REGULATION

研究表明，胰岛素可能是食物摄入的调节剂 通过作用于中枢神经系统（CNS）来减轻体重。 这 更新建议解决了胰岛素的能力， 在正常生长和发育过程中， 并且在肥胖症中可能是异常的。 建议进行研究， 无论是中枢神经系统的胰岛素摄取，还是中枢神经系统中的胰岛素作用， 在大鼠中作为年龄、性别和遗传或 饮食引起的肥胖 将在体内评估脑的胰岛素摄取 通过测量血浆和CSF胰岛素的稳态水平， 载体或胰岛素输注。 脑毛细血管胰岛素结合位点 将作为特异性受体介导的 运输能力。 这些受体的调节已被观察到， 这个实验室和其他实验室，可能代表了一种潜在的机制， 调节胰岛素摄取进入CNS。 胰岛素的作用将是 通过测量体重和食物摄入量进行行为评估， 对脑室内胰岛素输注的反应。 胰岛素体外作用 将通过测量胰岛素对去甲肾上腺素的影响进行评估 摄取和突触后事件在海马体，一个大脑区域， 我已经证明胰岛素刺激磷脂代谢 这可能是局部介导的儿茶酚胺，以及在 下丘脑和嗅球，这两个大脑区域发挥着主要的作用， 在调节食物摄入量和体重方面的作用，并与 外周胰岛素作用的变化。 总之，这些研究应该 确定候选CNS肥胖症的有效性 信号，胰岛素，是通过其摄取和/或作用的变化来调节的， CNS。

Studies have suggested that insulin may be a regulator of food intake and body weight by acting at the central nervous system (CNS). This renewal proposal addresses the hypothesis that the ability of insulin to act as a satiety signal may change during normal growth and development, and may be abnorrnal in obesity. Studies are proposed to examine whether insulin uptake into the CNS, or insulin action-in the CNS, is altered in rats as a function of age, gender, and genetic or diet-induced obesity. Insulin uptake by brain will be assessed in vivo by measurement of steady state levels of plasma and CSF insulin during vehicle or insulin infusions. Brain capillary insulin binding sites will be measured as an in vitro estimate of specific receptor-mediated transport capacity. Regulation of these receptors has been observed by this laboratory and others and may represent a potential mechanism for regulation of insulin uptake into the CNS. Insulin action will be assessed behaviorally by measuring body weight and food intake in response to intraventricular insulin infusions. Insulin action in vitro will be assessed by measurement of insulin effects on norepinephrine uptake and post-synaptic events in the hippocampus, a brain region in which I have demonstrated insulin stimulation of phospholipid metabolism which may be mediated locally by catecholamines, as well as in the hypothalamus and olfactory bulb, two brain regions which play a major role in the regulation of food intake and body weight, and compared with changes of peripheral insulin action. Together, these studies should determine whether the effectiveness of the candidate CNS adiposity signal, insulin, is regulated by changes in its uptake and/or action in the CNS.