GLUCOSE HOMEOSTASIS IN THE SURGICALLY ALTERED PANCREAS

胰腺的外科手术改变已被用作治疗 各种疾病过程。然而，对解剖学的理解 胰腺的改变可以改变术后的调节 碳水化合物的代谢尚不清楚。最近，胰腺移植已经 曾受雇于I型糖尿病，但对后遗症知之甚少 移植胰岛素的分泌是存在的。此应用程序寻求继续 我们使用三种手术模式所做的努力 了解术后血糖稳态和胰岛素的变化 分泌物。胰岛素分泌的明显变化似乎是因为 与移植相关的三个解剖改变中的一个：1。 胰岛β细胞质量减少，2.胰岛素在胰腺的全身释放 静脉流出物；3.去神经(自体移植)。我们的狗 手术模式已经通过静脉注射(IVGTT)和口服进行了评估 (OGTT)葡萄糖挑战。使用正常血糖和高胰岛素的研究 已经进行了高血糖钳夹手术。我们的初步调查结果是 提示葡萄糖的处置存在着不同程度的变化 内源性胰岛素水平的范围。胰腺全身性引流 恢复外周胰岛素的“正常”水平，但 外周血糖水平持续存在。钳制研究表明，敏感性 向内源性胰岛素减少。评估外周设备的研究 对外源性输入的胰岛素和肝脏葡萄糖输出量的敏感性 没有解释为什么会有这些变化。更多研究表明 提示胰岛素水平以外的因素(非胰岛素依赖型 葡萄糖处置)，以及可能的肠道激素GIP缺乏 (葡萄糖依赖的促胰岛素多肽)，或胰多肽 (PP)可以解释我们的发现。我们建议在三年内继续努力 区域。首先，我们希望继续评估胰岛素对葡萄糖的反应。 挑战和更彻底地检查肠道激素缺乏症。第二, 我们建议评估胰岛素释放的脉动模式，并 手术干预是否改变了正常的分泌模式 可以解释外周血糖水平的变化。第三，我们提出了研究 目的：评价免疫抑制剂环孢素A及其对慢性粒细胞白血病的疗效。 应用OUTERS行胰腺移植的相关外科改变 自体移植模型。这些研究将允许基本观察到 胰岛素释放的生理性糖调节。脉冲剂的研究进展 胰岛素的释放和环孢素的作用提供了独特的机会 评估术后(移植)对血糖稳态的影响。

Surgical alterations of the pancreas have been used as treatment for various disease processes. However, understanding of how anatomic alterations of the pancreas can change postoperative regulation of carbohydrate metabolism is unclear. Recently, pancreas transplantation has been employed for Type I diabetes, yet very little understanding of post- transplant insulin secretion exists. This application seeks continuation of our efforts using three surgical models which are relevant to understanding postoperative changes in glucose homeostasis and insulin secretion. Distinct changes in insulin secretion appear to result because of one of three anatomic alterations relevant to transplantation: 1. reduction of beta cell mass, 2. systemic release of insulin in pancreatic venous effluent, and 3. denervation (autotransplantation). Our canine surgical models have been evaluated using intravenous (IVGTT) and oral (OGTT) glucose challenge. Studies using euglycemic hyperinsulinemic and hyperglycemic clamps have been performed. Our preliminary findings have suggested that alteration in disposal of glucose exists over a varying range of endogenous insulin levels. Systemic drainage of the pancreas restores "normal" levels of insulin in the periphery, yet alterations in peripheral glucose levels persist. Clamp studies suggest that sensitivity to endogenous insulin is decreased. Studies to evaluate peripheral sensitivity to exogenously infused insulin and hepatic glucose output have not explained why these alterations exist. Additional studies have suggested that factors other than insulin levels (insulin-independent glucose disposal) and, possibly, the deficiency of an enteric hormone, GIP (glucose-dependent insulinotropic polypeptide), or pancreatic polypeptide (PP) may explain our findings. We propose to continue our efforts in three areas. First, we wish to continue evaluating insulin response to glucose challenge and examine more thoroughly enteric hormone deficiencies. Second, we propose to evaluate the pulsatile pattern of insulin release, and whether changes in normal secretory patterns by surgical interventions would explain altered peripheral glucose levels. Third, we propose studies to evaluate the immunosuppressive agent, cyclosporine, and its effect on the surgical alterations relevant to pancreas transplantation using our autotransplant model. These studies will allow basic observations about physiologic glucoregulation of insulin release. The studies on pulsatile release of insulin and cyclosporine effects offer unique opportunities to evaluate postsurgical (transplant) effects on glucose homeostasis.