PANCREATIC TRANSPLANTATION IN DIABETIC PATIENTS

本提案中描述的研究涉及临床研究 胰腺内分泌功能的异常生理调节， 在接受过以下治疗的I型糖尿病患者中的葡萄糖稳态 同种异体胰腺移植 由于移植胰腺没有 移植后的神经连接，这种手术程序提供了 一个独特的机会来研究神经调节的重要性， 内分泌胰腺 此外，由于这一手术过程导致 在静脉流出回流的异位移植胰腺中， 对于全身循环而不是门静脉循环，重要的是 完全理解这种异常回路的代谢后果。 实验包括评估胰岛素和C肽分泌， 对各种激动剂的反应，无和有葡萄糖增强作用; 肾上腺素能激动剂和阻断剂研究;以及胰岛素抵抗研究 使用正常血糖高胰岛素血症和高血糖钳夹。 的 实验还包括评估胰高血糖素对精氨酸的反应， 低血糖以及胰多肽对促胰液素的反应， 低血糖 还将在给药期间评估儿茶酚胺分泌。 肾上腺素能阻断和低血糖研究。 我们还建议评估 半胰腺切除术在一组非- 将一半胰腺捐赠给I型糖尿病患者的糖尿病受试者 受惠人士 这些研究旨在评估是否已经知道 供体的代谢异常处于高峰或是否持续 葡萄糖稳态的恶化将大于年龄匹配的 对照 在这项工作结束时，预计我们将 能够对神经调节的重要性提供独特的评估 内分泌胰腺以及更好地了解异常 移植一个去神经，异位定位的 I型糖尿病患者的移植胰腺。

The research described in this proposal involves clinical investigation into abnormal physiologic regulation of endocrine pancreatic function and glucose homeostasis in Type I diabetic patients who have undergone allograft pancreas transplantation. Since the allograft pancreas has no neural connections after transplantation, this operative procedure provides a unique opportunity to investigate the importance of neuroregulation of the endocrine pancreas. Moreover, since this operative procedure results in an ectopically situated allograft pancreas whose venous outflow returns to the systemic rather than the portal circulation, it is important to fully understand the metabolic consequences of this abnormal circuitry. The experiments involve evaluation of insulin and C-peptide secretion in response to various agonists without and with glucose potentiation; adrenergic agonist and blockade studies; and studies of insulin resistance using both euglycemic hyperinsulinemia and hyperglycemia clamps. The experiments also involve assessments of glucagon responses to arginine and hypoglycemia as well as pancreatic polypeptide responses to secretin and hypoglycemia. Catecholamine secretion will also be assessed during the adrenergic blockage and hypoglycemia studies. We also propose to evaluate the long-term consequences of hemi-pancreatectomy in a group of non- diabetic subjects who donated half of their pancreases to Type I diabetic recipients. These studies are designed to assess whether already known metabolic abnormalities in donors are at their peak or whether continued deterioration in glucose homeostasis will be greater than age-matched controls. At the conclusion of this work, it is anticipated that we will be able to provide a unique assessment of the importance of neuroregualtion of the endocrine pancreas as well as a better understanding of the abnormal metabolic consequences of transplanting a denervated, ectopically located allograft pancreas in Type I diabetic patients.