Mechanisms to Induce Islet Proliferation

诱导胰岛增殖的机制

基本信息

批准号：
8133036
负责人：
Patrick T. Fueger
金额：
$ 30.71万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8133036
关键词：
Address Animals Apoptosis Applications Grants Autoimmune Process Award Beta Cell Cadaver Cell Line Cell Proliferation Cell physiology Cells Development Diabetes Mellitus Disease EGF gene Epidermal Growth Factor Receptor Equilibrium Faculty Genes Glucagon Glucose Goals Graduate Education Growth Growth Factor Harvest Indiana Insulin Insulin-Dependent Diabetes Mellitus Islets of Langerhans Islets of Langerhans Transplantation K-Series Research Career Programs Laboratories Lead Learning Mentors Methods Modeling Molecular and Cellular Biology Non-Insulin-Dependent Diabetes Mellitus Pancreas Pancreatic Hormones Pathway interactions Patients Pediatric Research Peptide Hydrolases Peptides Physiological Positioning Attribute Rattus Receptor Signaling Research Research Personnel Resistance Role S-Phase Fraction Signal Pathway Signal Transduction Source Structure of beta Cell of islet Transplantation Treatment Efficacy Universities Work base blood glucose regulation cell growth efficacy testing improved indexing islet medical schools member novel post-doctoral training programs research study stem treatment strategy trefoil factor

项目摘要

Glucose hofrieostasis is prirharlly maintained by the intricate bsilance of the glucoregiilatory, pancreatic hormones insulin and glucagon. Type 1 diabetes meljitus resijlts fironn the autoimmune destruction of pancreatic beta cells vt/h|ch produce insulin. Currently, the onjy available cure for type 1 diabeties is pancreatic or iislet transplantation, A prihriary linnitatJbn of theise bona fide cures is the limited availability of pancreataand paricreatic islets from cadaver donors. Because of thjs bottleneck, much work has been perfonned with the goal of finding an aiternative source of insulin-producing cells as well as establishing riiethpds to stimulate proliferation bf islets harvissted for transplantation. The current application addresses the critical need to establish methods to increase pancreatic islet mass. If successful, nfiore patients with type 1 diabetes will benefit from islet transplantation and be free from this serious disease. We have recently discovered that the pf-btease-reslstant peptide trefoil factor 3 (TFF3) is a jgrpwth factor for pancreatic islets. Since the discovery of TFFS's ability to increase cell proliferation of pancreatic beta cells, vt/e have begun to uncover the signaling pathways that lead tO: this beneficial effect. However, much work remains to fully characterize these pathways and to perhaps reveal other pathways that can be exploited in order tb Increase pancreatic beta cell tmiass. Further, it is equallylmportantto continue to identify novel factors that have the abiJify to increase beta cell mass. In pursuit of these goals.the following specific aims are proposed: 1) to determine the role of EGFlreceptor signaling on TFF-3 induced beta cell proliferation, 2) to determine the ro\e of Gene 33/Mig-6/RALT in mbdulatlng EGF receptcr signaling and beta cell proliferation, and 3) to identify noverfactors that regulate pancreatic beta cell mass. The results of this work might increase the therapeutic efficacy of islettrahsplant^tlpn.:

血糖稳定主要是通过葡萄糖调节、胰腺激素胰岛素和胰高血糖素的复杂平衡来维持的。 1 型糖尿病可抵抗产生胰岛素的胰腺 β 细胞的自身免疫破坏。目前，治疗 1 型糖尿病的唯一可用方法是胰腺或胰岛移植。这些真正治愈的主要障碍是来自尸体捐赠者的胰腺和胰岛胰岛的可用性有限。由于这一瓶颈，人们进行了大量的工作，目的是寻找胰岛素产生细胞的替代来源以及建立刺激用于移植的胰岛增殖的细胞。当前的申请解决了建立增加胰岛质量的方法的迫切需要。如果成功，nfiore 1 型糖尿病患者将受益于胰岛移植并免受这种严重疾病的困扰。我们最近发现，抗 pf-btease 肽三叶因子 3 (TFF3) 是胰岛的 jgrpwth 因子。自从发现 TFFS 能够增加胰腺 β 细胞的增殖能力以来，vt/e 已经开始揭示导致 tO 的信号传导途径：这种有益的作用。然而，仍有许多工作要做，以充分表征这些途径，并可能揭示可用于增加胰腺β细胞活性的其他途径。此外，继续鉴定能够增加β细胞质量的新因子也同样重要。为了实现这些目标，提出了以下具体目标：1)确定EGF1受体信号转导对TFF-3诱导的β细胞增殖的作用，2)确定基因33/Mig-6/RALT在调节中的作用EGF 受体信号传导和 β 细胞增殖，以及 3) 识别调节胰腺 β 细胞质量的非因子。这项工作的结果可能会提高 islettrahsplant^tlpn 的治疗效果：