Pathobiology of the Enteric System

糖尿病患者的胃排空障碍、进食障碍和特发性疾病是发病率的重要原因。目前有效管理胃排空障碍的方法是无效的。该计划项目的目的是促进我们对胃肌肉系统营养不良变化的理解，以及导致胃排空障碍和胃运动障碍的反馈机制，并开发预防或逆转这些变化并恢复胃排空的策略，这些策略可在人体临床试验中进行测试。科学目标通过三个高度整合的项目和三个核心来实现。项目1(糖尿病胃肠病的病理生物学)研究HO1在预防糖尿病胃轻瘫发展中的作用以及调节糖尿病患者HOI活性的机制。项目2(慢性热量限制中胃功能障碍的机制)研究慢性或慢性间歇性热量缺乏相关的运动障碍中胃肌肉细胞营养不良的作用，以及营养不良的变化是否由IGF-1和HO-1的产生减少所介导。项目3(糖尿病肠病的神经体液调节)在临床试验中评估HO1表达增加对糖尿病患者胃排空的影响，评估血糖控制对糖尿病患者胃排空的影响，并确定导致胃底松弛受损和快速胃排空的十二指肠-胃反馈受损的机制。行政核心A将领导所有计划项目活动。成像核心B将提供先进的软件，用于体内和体外成像的严格定量分析，以及患者胃部的动态磁共振成像。生理特征和数据管理核心C将开发和管理电子动物研究记录，使所有计划调查人员都可以在一个电子记录中获得所有研究数据。这一高度整合的计划将在理解胃排空障碍的肠道系统病理生物学方面取得重大进展，并将这些知识转化为新的诊断工具和治疗方法。

Disorders of gastric emptying in patients with diabetes, eating disorders and in idiopathic conditions are a significant cause of morbidity. Current approaches for effectively managing gastric emptying disorders are ineffective. The objective of this Program Project is to advance our understanding of the dystrophic changes in the gastric musculature and feed back mechanisms that are the cause of disorders of gastric emptying and gastric motor disturbances and develop strategies to prevent or reverse these changes and restore gastric emptying that are testable in human clinical trials. The scientific objectives are met through three highly Integrated projects and three cores. Project 1 (Pathobiology of Diabetic Gastroenteropathy) studies the role of HO1 in preventing the development of diabetic gastroparesis and the mechanisms that regulate HOI activity in diabetes. Project 2 (Mechanisms of Gastric Dysfunction in Chronic Caloric Restriction) studies the role of cellular dystrophy in the gastric musculature in dysmotilities associated with chronic or chronic intermittent caloric deficit and whether the dystrophic changes are mediated by reduced production of IGF-1 and HO-1. Project 3 (Neurohumoral Regulation in Diabetic Enteropathy) evaluates in clinical trials the effect of increasing HO1 expression on gastric emptying in patients with diabetes, assesses the Impact of glycemic control on gastric emptying in diabetic patients and determines the mechanism accounting for Impaired duodenal-gastric feedback responsible for impaired fundic relaxation and rapid gastric emptying. The Administrative Core A will provide leadership of all Program Project activities. The Imaging Core B will provide advanced software for rigorous quantitative analysis for in vivo and in vitro imaging, and dynamic MR imaging on the stomach in patients. The Physiological Characterization and Data Management Core C will develop and manage an Electronic Animal Research Record that makes available In a single electronic record all research data to all Program investigators. This highly-integrated Program will make significant progress toward understanding the pathobiology of the enteric system in gastric emptying disorders and translate this knowledge into new diagnostic tools and therapy.