INTRA-ISLET COMMUNICATION IN SURGICALLY ALTERED PANCREAS

初步数据表明存在自动调节反馈循环 在人类胰岛内：胰岛素刺激生长抑素，并且 生长抑素抑制胰岛素分泌。 此第一条的目的 奖励项目旨在证明胰岛素和生长抑素 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 和针对胰岛素的抗体的Fab片段和 生长抑素将用于分离灌注的人和大鼠胰腺 模型。 这些模型允许进行细胞间研究 与保存胰岛微血管的通讯。 胰岛素和 生长抑素分泌反应将使用无线电测量 免疫测定技术。 生长抑素和胰岛素 mRNA 转录 将使用 Northern blot 技术进行表征。 扩散 可检查 FITC 抗体和 FITC-Fab 片段的特征 利用体内显微镜大鼠胰腺模型。 本提案中的实验有以下具体目标： 1. 确定胰岛内生长抑素是否是一种抑制介质 胰岛素分泌； 2. 确定胰岛内胰岛素是否为 生长抑素分泌的刺激介质； 3. 确定 胰岛内胰岛素是否调节生长抑素的转录 信使RNA； 4. 确定胰岛内生长抑素是否调节 胰岛素 mRNA 的转录； 5. 判断是否有抗体 抗体的 Fab 片段离开血管内隔室 并进入胰岛间质。 这项研究的意义在于获得更好的理解 胰岛生理学。 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.