PANCREATIC TRANSPLANTATION IN DIABETIC PATIENTS

本提案中所述的研究涉及临床调查。 内分泌胰腺功能的异常生理调节和 I型糖尿病患者服药后血糖稳态的变化 同种异体胰腺移植。因为同种异体胰腺没有 移植后的神经连接，这个手术程序提供了 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，由于这一手术过程的结果是 静脉流出回流的异位移植胰腺 对于全身循环而不是门脉循环，重要的是 充分了解这种异常回路的新陈代谢后果。 这些实验包括评估胰岛素和C肽的分泌。 对各种激动剂的反应，无葡萄糖增强和有葡萄糖增强； 肾上腺素能激动剂和阻滞剂的研究；胰岛素抵抗的研究 同时使用正常血糖、高胰岛素血症和高血糖钳夹。这个 实验还包括评估胰高血糖素对精氨酸和 胰泌素和胰岛多肽对低血糖和胰多肽的反应 低血糖症。儿茶酚胺的分泌量也将在 肾上腺素能阻断和低血糖研究。我们还建议评估 非胰腺癌患者行半胰腺切除术的远期疗效 将一半胰腺捐献给I型糖尿病患者的糖尿病患者 收件人。这些研究旨在评估是否已知 捐献者的代谢异常达到顶峰或是否继续 血糖稳态的恶化将比年龄匹配的更严重 控制。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 以及更好地了解内分泌胰腺的异常 异位失神经移植的代谢后果 I型糖尿病患者的同种异体胰腺移植

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.