PANCREAS AND ISLET TRANSPLANTATION IN HUMANS

“这项提案所述工作的总目标是充分 了解长期、成功的胰腺的代谢后果 和胰岛移植在1型糖尿病患者中的应用 健康人半胰腺切除的长期代谢后果 人类捐赠者。对于胰腺移植的接受者来说，这两种 具体目标是：具体目标1：比较胰岛素分泌储备 接受环孢素或FK 506的胰腺移植受者 作为免疫抑制疗法。具体目标2：评估反 低血糖时胰高血糖素和肾上腺素的调节反应 移植前和移植后纵向高胰岛素钳夹 并确定患者的反应是否存在差异 接受环孢素或FK506。对于经历过的正常患者 半个胰腺切除术将半个器官捐献给亲属，两个特定 目标是特定的目标3：评估血糖调节和胰岛素 术前、术后纵向分泌性储备 在捐赠者身上。具体目标4：评估胰岛素介导的葡萄糖处置， 葡萄糖介导的葡萄糖处置和血糖调节 健康人体供体手术后的纵向和纵向研究。 对于接受自体或同种异体胰岛移植的1型患者， 三个具体目标是：具体目标5：将 移植后胰岛素分泌储备与胰岛数目的关系 自身移植在非糖尿病慢性胰腺炎患者中的应用 特定目标6：比较血糖调节和胰岛素分泌 接受或不接受类固醇治疗的胰岛受者的纵向储备 类固醇和环孢素或FK 506。具体目标7：评估胰高血糖素 术前低血糖、高胰岛素钳夹的反应 而在接受同种异体胰岛治疗的1型糖尿病患者中，则是纵向的。这个 实现这些目标的研究设计和方法将包括 测定血糖、糖化血红蛋白、胰岛素、C肽、 和胰高血糖素分泌；低血糖、高胰岛素血症和正血糖， 高胰岛素血症(同时输注和不输注生长抑素) 精氨酸诱导胰岛素对葡萄糖增强作用的研究 分泌物。“

"The overall goal of the work described in this proposal is to fully understand the metabolic consequences of long term, successful pancreas and islet transplantation in Type 1 Diabetic patients and to ascertain the long term metabolic consequences of hemi pancreatectomy in healthy human donors. For recipients of pancreas transplantation, the two specific aims are: Specific Aim 1: To compare insulin secretory reserve in pancreas transplant recipients receiving either cyclosporin or FK 506 as immunosuppressive therapy. Specific Aim 2: To assess counter- regulatory responses of glucagon and epinephrine during hypoglycemic, hyperinsulinemic clamps pretransplant and longitudinally posttransplant and to ascertain whether differences in responses exist in patients receiving cyclosporin or FK506. For normal patients who have undergone hemi pancreatectomy to donate hemi organs to relatives, the two specific aims are Specific Aim 3: To assess glycemic regulation and insulin secretory reserve pre operatively and longitudinally post operatively in donors. Specific Aim 4: To assess insulin mediated glucose disposal, glucose mediated glucose disposal, and glycemic regulation pre operatively and longitudinally post operatively in healthy human donors. For type 1 patients receiving auto or allotransplantation of islets, the three specific aims are: Specific Aim 5: To correlate measurements of post transplant insulin secretory reserve with the number of islets autotransplanted in non diabetic chronic pancreatitis patients. Specific Aim 6: To compare glycemic regulation and insulin secretory reserve longitudinally in islet recipients receiving steroids or no steroid and cyclosporin or FK 506. Specific Aim 7: To assess glucagon responses during hypoglycemic, hyperinsulinemic clamps pre operatively and longitudinally in type 1 diabetic patients receiving alloislets. The research design and methods for achieving these goals will include measurements of glucose and hemoglobin AlC levels; insulin, C peptide, and glucagon secretion; hypoglycemic, hyperinsulinemic and euglycemic, hyperinsulinemic (with and without concurrent somatostatin infusion) clamps; and studies of glucose potentiation of arginine induced insulin secretion."