GLUCOSE HOMEOSTASIS AND THE SURGICALLY ALTERED PANCREAS

胰岛素释放的糖调节在两种疾病中都知之甚少 正常的完整生物体以及那些被疾病改变的生物体 流程。手术改变模型的慢性研究 胰腺有助于了解某些疾病的过程 (减少的β细胞质量-糖尿病)以及 外科手术治疗(胰腺移植)。我们的预赛 研究结果已经记录了门户到 全身性胰岛素释放及“非胰岛素依赖”效应 关于外周葡萄糖的处理。这些观察结果具有相关性 在评估三种胰腺手术改变时， 有病理生理后果--β细胞质量减少(80% 胰腺切除)，全身胰岛素释放(脾-腔静脉 分流)和去神经(自体移植)。这项建议 打算通过继续扩展我们的初步调查结果 静脉和口服葡萄糖激发对慢性阻塞性肺疾病的疗效观察 手术改变的胰腺模型。此外，我们 建议进行更深入的研究，以便对 门静脉“去绝缘”后的肝脏葡萄糖输出量。 磺脲类药物对胰岛β细胞质量减少的反应 将研究治疗方法。使用“稳定状态”的研究 将进行高血糖葡萄糖输注以研究 抑制(生长抑素)的多肽的调节作用 刺激(GIP)胰岛素分泌。最后，继续研究 不依赖于胰岛素的葡萄糖处理将允许进一步 对似乎是很大一部分葡萄糖的理解 在没有的情况下在外围设备中进行的处理 荷尔蒙。我们将确定这是否解释了 手术治疗已经记录在案的葡萄糖处置后的变化- 从操作上讲。这项研究将使我们能够对 胰岛素释放的生理性糖调节以及 胰腺手术改变的后果可能 受雇于疾病的治疗过程。

Glucoregulation of insulin release is poorly understood both in normal intact organisms as well as those altered by disease processes. Chronic studies of models of the surgically altered pancreas allow understanding of certain disease processes (reduced beta cell mass - diabetes) as well as applicability of surgery in treatment (pancreas transplantation). Our preliminary findings have documented the important consequences of portal to systemic release of insulin as well as "insulin-independent" effects on peripheral glucose disposal. These observations have relevance in evaluating three surgical alterations of the pancreas which have pathophysiologic consequence - reduced beta cell mass (80% pancreatectomy), systemic release of insulin (spleno-caval diversion) and denervation (autotransplantation). This proposal intends to expand our preliminary findings by continued observations of intravenous and oral glucose challenge on chronic models of the surgically altered pancreas. Additionally, we propose further studies that allow more sophisticated analysis of hepatic glucose output after "de-insulination" of the portal vein. The response of decreased beta cell mass to sulfonylurea treatment will be studied. Studies employing "steady state" hyperglycemic glucose infusions will be done to study the modulating effects of peptides which suppress (somatostatin) or stimulate (GIP) insulin secretion. Finally, continued studies on "insulin-independent" glucose disposal will allow further understanding of what appears to be a large fraction of glucose handling in the periphery which occurs in the absence of the hormone. We will determine whether this explains the effects of surgery on already documented changes in glucose disposal post- operatively. This studies will allow basic observations about physiologic glucoregulation of insulin release as well as the consequences of surgical alterations of the pancreas which might be employed for treatment of disease processes.