INTRA-ISLET COMMUNICATION IN SURGICALLY ALTERED PANCREAS

初步数据显示存在一个自动调节反馈环路 在人类胰岛内：胰岛素刺激生长抑素，以及 生长抑素抑制胰岛素的分泌。这第一个目的是 获奖项目是证明胰岛素和生长抑素是 胰岛细胞分泌的胰岛内介质。 激素输注和抗体免疫中和技术 和针对胰岛素和胰岛素的抗体的Fab片段 生长抑素将用于人和大鼠的离体胰腺灌流 模特们。这些模型允许细胞对细胞的体外研究。 与胰岛微血管保存的沟通。胰岛素和 生长抑素的分泌反应将使用无线电测量- 免疫分析技术。生长抑素与胰岛素基因转录 将使用Northern印迹技术对其进行表征。扩散 可检测FITC抗体和FITC-Fab片段的特性 利用活体显微镜下的大鼠胰腺模型。 这项建议中的实验有以下具体目的：1. 确定胰岛内生长抑素是否是糖尿病的抑制介质 胰岛素分泌；2.确定胰岛内胰岛素是否是一种 刺激调节生长抑素的分泌；3.测定 胰岛内胰岛素是否调节生长抑素的转录 4.确定胰岛内生长抑素是否调节 转录胰岛素信使核糖核酸；5.测定抗体 抗体的Fab片段离开血管内隔间 进入胰岛的间质。 这项研究的意义在于更好地了解 关于胰岛生理学的研究。此外，我们预计这些技术 将用于研究移植的胰岛。

Preliminary data suggests there exists an autoregulatory feedback loop within the human islet: insulin stimulates somatostatin, and somatostatin inhibits insulin secretion. The purpose of this First Award project is to demonstrate that insulin and somatostatin are intraislet mediators of islet cell secretion. Hormonal infusions and immunoneutralization techniques with antibodies and Fab fragments of antibodies directed against insulin and somatostatin will be used in isolated perfused human and rat pancreas models. These models allow for in vitro studies of cell-to-cell communication with preservation of islet microvasculature. Insulin and somatostatin secretory responses will be measured using radio- immunoassay techniques. Somatostatin and insulin mRNA transcription will be characterized using Northern blot technique. Diffusion characteristics of FITC-antibody and FITC-Fab fragments can be examined utilizing an in vivo microscopy rat pancreas model. The experiments in this proposal have these specific aims: 1. To determine whether intraislet somatostatin is an inhibitory mediator of insulin secretion; 2. To determine whether intraislet insulin is a stimulatory mediatory of somatostatin secretion; 3. To determine whether intraislet insulin regulates the transcription of somatostatin mRNA; 4. To determine whether intraislet somatostatin regulates the transcription of insulin mRNA; 5. To determine whether the antibodies and Fab fragments of the antibodies leave the intravascular compartment and enter the interstitium of the islet. The significance of this study is in obtaining a better understanding of islet physiology. Furthermore, we anticipate that these techniques will be used to study the transplanted islet.