INTESTINAL MUCOSAL FUNCTION IN DIABETES

大鼠中不受控制的糖尿病导致多种 改变刷状缘膜的功能， 肠上皮细胞包括主动转运的刺激 各种膜结合的机制和增加 水解酶 阐明所涉及的机制可能提供 对人类疾病的病理生理学的重要见解 以及对刷毛边境管制的性质 proteins. 我们的长期目标是阐明这些 机制等 我们的具体目标是回答以下问题 问题：（1）蔗糖酶的生物合成速率增加- 糖尿病动物体内的异麦芽糖酶是转录的结果， 翻译或翻译后变化;（2）是变化 具体的或有改变所有刷状边界的规定 水解酶;（3）调节改变的介质是什么;（4） 是在其他情况下水解酶的改变， 糖尿病的变化 为了回答这些问题，我们将研究 糖尿病和其他水解酶活性 在前体的合成和细胞内加工上发生改变 选择画笔边缘水解酶。会来做这项工作 脉冲/追踪实验，随后免疫沉淀， SDS-聚丙烯酰胺凝胶电泳和荧光法 免疫电镜 对mRNA水平的影响 在无细胞翻译实验中寻找，以及 几种可能的介质在器官的生物合成过程中， 培养的肠确定。 最后，由于细胞内 这些蛋白质的加工过程还不完全清楚，我们将， 在这些实验的过程中， 在正常大鼠肠道中的处理，并且在一些情况下， 水解酶，人类肠道。

Uncontrolled diabetes mellitus in the rat results in multiple alterations in the function of the brush border membrane of the enterocyte including the stimulation of active transport mechanisms and increases in a variety of membrane-bound hydrolases. Elucidation of the mechanisms involved may provide important insight into the patho-physiology of the human disease as well as into the nature of the regulation of brush border proteins. Our long term objective is to elucidate these mechanisms. Our specific aims are to answer the following questions: (1) is the increased rate of biosynthesis of sucrase- isomaltase in diabetic animals the result of transcriptional, translational, or posttranslational changes; (2) are the changes specific or is there altered regulation of all brush border hydrolases; (3) what are the mediators of altered regulation; (4) are alterations in hydrolases in other situations related to the diabetic changes. To answer these questions we will study the effects of diabetes and other conditions where hydrolase activity is altered on synthesis and intracellular processing of precursors of selected brush border hydrolases. This will be done by pulse/chase experiments followed by immune precipitation and SDS-polyacrylamide gel electrophoresis and fluorography and by immunoelectron microscopy. Effects on mRNA levels will be sought in cell free translational experiments, and the effects of several possible mediators on biosynthetic processes in organ- cultured intestine determined. Finally, since intracellular processing of these proteins is incompletely understood, we will, in the course of these experiments, define more clearly this processing in normal rat intestine and, in the case of several hydrolases, human intestine.