Mechanisms regulating nutrient induced motor patterns in the isolated small intestine

小肠的运动对于食物的消化和吸收是必不可少的，并且在饭后3-4小时内包括两种基本模式。这些是混合（或分割）和推进（或融合）。虽然这是正在进行的研究的主题，但对控制推进的基本机制了解很多，主要是因为这种行为很容易在肠道的孤立部分中看到，因此可以进行高度控制的实验来识别系统的各种细胞成分。相比之下，只有在完整的动物中才能可靠地看到混合，这使得研究这种行为的详细机制变得更加困难。我们所知道的是，膳食的组成控制着小肠沿着任何位置的混合和推进的相对量。我们最近发现了一种在离体小肠（十二指肠和/或空肠）中的收缩模式，该模式是由肠中存在的营养物质引起的，并且与在完整动物中观察到的混合行为非常相似。我们已经证明，这种模式取决于神经细胞的活动，包括那些兴奋肠道肌肉的细胞，它取决于脂肪和其他营养物质从肠壁内壁释放的激素的活动。这项建议的目的是确定营养物质如何相互作用以产生这种收缩模式，特定类型的神经细胞的相对作用以及营养物质释放的局部激素作用的部位。这一点很重要，因为增加混合推进的比例可以增强膳食中营养素的吸收，因此，如果启动混合行为的机制可以通过特定的营养素以可预测的方式进行调节，则可以增强各种吸收不良综合征的吸收。

The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the various cellular components of the system. By contrast, mixing has only been reliably seen in intact animals making studies of the detailed mechanisms responsible for this behaviour much more difficult. What is known is that the composition of a meal controls the relative amount of mixing and propulsion seen at any location along the small intestine. We have recently identified a pattern of contractions in isolated small intestine (duodenum and-or jejunum) that is induced by the presence of a nutrient in the intestine and appears very similar to the mixing behaviour seen in the intact animal. We have shown that this pattern depends on the activity of nerve cells including those that excite the gut muscle and that it depends on the activity of a hormone released from the lining of the gut wall by fats and other nutrients. The aims of this proposal are to identify how nutrients interact to produce this pattern of contractions, the relative roles of specific types of nerve cells and the sites at which the local hormones released by nutrients act. This is important because increasing the proportion of mixing to propulsion enhances the absorption of nutrient from a meal, so if the mechanisms that initiate mixing behaviour can be regulated in a predictable way by specific nutrient, absorption can be enhanced in various malabsorption syndromes.