PEPTIDE YY--COLONIC GASTRIC AND PANCREATIC INHIBITION

目的是建立新发现的回结肠肽， 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，研究将在犬中进行。 第一系列 实验将检查PYY的释放机制。 我们尤其 将决定来自上肠的神经或激素信息 确定PYY的释放或是否与营养物质直接接触， 回结肠粘膜是释放的必要先决条件。 未来 通过一系列实验，我们将研究外源性注入的影响， 肽YY对胰泌素、胆囊收缩素的胰腺分泌反应 和假喂食 其他研究将检查PYY对胃粘膜的影响。 排空液体和固体食物。 在这些研究中， 将外源性PYY输注期间观察到的PYY与 观察餐后和肠灌注油酸后， 确定这些影响是药理学的还是生理学的。 我们 最近证明，PYY特异性地抑制了 酸分泌 为了确定PYY的生物学行为是否是迷走神经的， 我们将检查迷走神经切断术对PYY能力的影响， 抑制胃和胰腺分泌。 在其他实验中，我们将 用油酸灌注回肠和结肠，并监测对 胰腺和胃分泌以及血浆肽YY浓度。 将为其他动物准备肠插管，以便 肠内容物可以转移到回肠上方，以确定 回结肠阻断对餐后胃和胰腺功能的影响 分泌和PYY释放。 在每种情况下观察到的PYY血液水平 然后通过输注外源性PYY来再现实验条件 为了确定PYY是否解释了回肠灌注后的分泌改变， 油酸或回肠旁路。 代谢清除率研究将在 以确定PYY的代谢半衰期是否与 胃肠激素的作用。 最后，犬PYY将 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。 要建立 PYY是一种具有独特特性的肠抑胃素。 最后，他们会 确定PYY是否是回结肠胰腺抑制剂， “胰蛋白酶”或其他人描述的“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.