INTRA-ISLET COMMUNICATION IN SURGICALLY ALTERED PANCREAS

初步数据表明存在一个自动调节反馈回路 在人体胰岛内：胰岛素刺激生长抑素， 生长抑素抑制胰岛素分泌。 第一次会议的目的 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 和针对胰岛素的抗体的Fab片段， 生长抑素将用于离体灌注的人和大鼠胰腺 模型 这些模型允许在体外研究细胞与细胞之间的相互作用。 与胰岛微血管的保存相联系。 胰岛素和 生长抑素分泌反应将使用放射- 免疫测定技术。 生长抑素和胰岛素mRNA转录 将使用北方印迹技术表征。 扩散 可以检查FITC-抗体和FITC-Fab片段的特征 利用体内显微镜大鼠胰腺模型。 本提案中的实验具有以下具体目标：1. 到 确定胰岛内生长抑素是否是 胰岛素分泌; 2. 为了确定胰岛内胰岛素是否是 生长抑素分泌的刺激介导; 3. 以确定 胰岛内胰岛素是否调节生长抑素的转录 mRNA; 4. 为了确定胰岛内生长抑素是否调节 胰岛素mRNA的转录; 5. 为了确定抗体是否 抗体的Fab片段离开血管内室 然后进入小岛的中央。 这项研究的意义在于更好地了解 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.