PEPTIDE YY-COLONIC GASTRIC AND PANCREATIC INHIBITOR

目标是建立新发现的回肠结肠肽，多肽 YY(PYY)，作为一种真正的激素。由于PYY尚未被批准用于人类 受试者，研究将在狗身上进行。第一个系列 实验将检测PYY的释放机制。特别是，我们 将决定来自上肠道的神经或激素信息 确定PYY释放或营养素是否直接接触 回肠结肠粘膜是释放的必要前提。在下一个 在一系列实验中，我们将考察外源性输注的效果 YY肽对促胰液素、胆囊收缩素诱导的胰腺分泌反应的影响 和假喂食。其他研究将检验PYY对胃部的影响 清空液体和固体食物。在这些研究中，循环中的水平 将外源PYY注入过程中观察到的PYY与 观察餐后及肠道灌流后油酸的变化 确定这些影响是药理学的还是生理学的。我们 最近证实，PYY特异性地抑制了头部阶段的 胃酸分泌。以确定PYY的生物行为是否具有迷走性 我们将研究迷走神经切断术对PYY能力的影响 抑制胃和胰腺分泌。在其他实验中，我们将 用油酸灌流回肠和结肠，并监测其对 胰腺和胃分泌物与血浆多肽YY浓度的关系。 更多的动物将准备好肠道插管，以便 肠道内容物可以在回肠上方分流，以确定 回结肠离断术对餐后刺激胃和胰腺的影响 分泌和PYY释放。每种情况下观察血液中PYY的水平 然后通过输注外源PYY来重现实验条件 目的：确定PYY能否解释回肠灌流后分泌物的改变。 油酸或回肠搭桥术。届时将进行代谢清除研究 以确定PYY的代谢半衰期是否与 已经形成的胃肠激素。最后，狗狗PYY将会是 提取、纯化并测定氨基酸序列。这些研究 将决定PYY是否具有生理或病理生理作用 作为胃和胰腺分泌的调节剂。他们应该建立 PYY是一种具有独特特性的肠胃泌素。最后，他们会 确定PYY是否是回结肠胰腺抑制物， “胰腺激素”，或其他人所描述的“抗CCK激素”。

The goal is to establish the newly discovered ileo-colonic peptide, Peptide YY (PYY), as a true hormone. As PYY has not been approved for use in human subjects, studies will be performed in dogs. The first series of experiments will examine mechanisms of release of PYY. In particular, we will determine whether neural or hormonal messages from the upper intestine determine PYY release or whether direct contact of nutrients with the ileo-colonic mucosa is a necessary prerequisite for release. In the next series of experiments, we will examine the effects of exogeneously infused Peptide YY on th pancreatic secretory response to secretin, cholecystokinin and sham feeding. Other studies will examine the effects of PYY on gastric emptying of liquid and solid meals. In these studies circulating levels of PYY observed during infusion of exogeneous PYY will be compared to those observed after a meal and after the intestinal perfusion of oleic acid to determine if these effects are pharmacological or physiological. We recently demonstrated that PYY specifically inhibits the cephalic phase of acid secretion. To determine if PYY's biological actions are vagal dependent we will examine the effects of vagotomy on PYY's ability to inhibit gastric and pancreatic secretion. In other experiments we will perfuse the ileum and colon with oleic acid and monitor the effects on pancreatic and gastric secretion and on plasma peptide YY concentrations. Additional animals will be prepared with intestinal cannulas so that intestinal contents can be diverted above the ileum to determine the effects of ileo-colonic exclusion on meal stimulated gastric and pancreatic secretion and PYY release. Blood levels of PYY observed under each experimental condition will then be reproduced by infusion of exogenous PYY to determine if PYY explains the altered secretion after ileal perfusion of oleic acid or ileal bypass. Metabolic clearance studies will then be performed to determine if PYY has a metabolic half life comparable to that of established gastrointestinal hormones. Finally, canine PYY will be extracted, purified and the amino acid sequence determined. These studies will determine whether PYY has a physiological or pathophysiological role as a modulator of gastric and pancreatic secretion. They should establish PYY as an enterogastrone with unique characteristics. Finally, they will determine if PYY is the ileo-colonic pancreatic inhibitor, the "pancreatone", or "anti-CCK hormone" described by others.