ENTEROGLUCAGON AND INTESTINAL ADAPTATION

该项目的目的是确定肠胰高血糖素作为一种 肠道适应的体液介质。肠道长期以来 已知表现出两种不同类型的适应。一、肠道 粘膜质量增加，因此所有营养物质的吸收增加， 在许多与增加的能量需求相关的条件下， 食欲过盛第二，特定的肠道转运蛋白是向上的-或 通过饮食水平或体内储存的 印刷受体.强烈的暗示但不是决定性的证据使它很可能 肠胰高血糖素是一种前一种反应的体液介质， 并且在饮食的情况下也可能有助于后一种反应 碳水化合物对肠道葡萄糖转运蛋白的影响。因此这个项目 将通过体内研究测试肠胰高血糖素在适应中的作用 在老鼠身上，采用了关键的测试，这些测试直到 最近由于缺乏对内源性肠胰高血糖素形式的了解， 它们用于体内测试的有限可用性和不充分的测定。一 方法将是测试两种慢性输注的效果， 肠胰高血糖素肽、胃泌酸调节素和GLP-1 7-36酰胺对粘膜 生长和肠道营养吸收。另一种方法是 测试免疫中和肠胰高血糖素对两种类型的 在这个实验室开发的两个大鼠模型中进行了适应。之一 模型产生了几倍的粘膜质量增加，另一个模型 葡萄糖转运蛋白活性增加两倍。健康相关性 这个项目的作用来自肠道适应的重要性， 临床状况，如糖尿病，短肠综合征，妊娠， 哺乳和锻炼。

This project's objective is to identify the role of enteroglucagon as a humoral mediator of intestinal adaptation. The intestine has long been known to exhibit two distinct types of adaptation. First, intestinal mucosal mass increases, and hence absorption of all nutrients increases, under many conditions associated with increased energy needs leading to hyperphagia. Second, specific intestinal transporters are up- or down-regulated by changes in dietary levels or body stores of their substrates. Strongly suggestive but not conclusive evidence makes it likely that enteroglucagon is a (the?) humoral mediator of the former response, and may also contribute to the latter response in the case of dietary carbohydrate effects on intestinal glucose transporters. Hence this project will test enteroglucagon's role in adaptation by means of in vivo studies in rats, employing critical tests that could not be carried out until recently because of lack of knowledge of endogenous enteroglucagon forms, their limited availability for in-vivo testing, and inadequate assays. One approach will be to test the effects of chronic infusions of two enteroglucagon peptides, oxyntomodulin and GLP-1 7-36 amide, on mucosal growth and on intestinal nutrient uptake. The other approach will be to test the effect of immunoneutralizing enteroglucagon on both types of adaptation in two rat models that this laboratory developed. One of the models produces a several-fold increase in mucosal mass, the other a two-fold increase in glucose transporter activity. The health relatedness of this project derives from the role of intestinal adaptation in important clinical conditions, such as diabetes, short bowel syndrome, pregnancy, lactation, and exercise.