Obese diabetic rat model w/o leptin/leptin-receptor defe

项目概述/摘要：美国估计有1820万人（占人口的6.3%）患有糖尿病；90%至95%的确诊病例为II型糖尿病（NIDDK， 2005年）。寻找新的和更有效的治疗方法来解决越来越多的美国II型糖尿病及相关疾病，目前由于缺乏与人类糖尿病状况非常相似的研究动物模型而受到阻碍。目前市面上所有与代谢综合征和显性II型糖尿病相关的大鼠模型都存在瘦素受体的遗传缺陷。相反，瘦素和瘦素受体缺陷并不是人类肥胖和糖尿病的常见病因。没有这种缺陷的大鼠模型将更接近于人类的情况，因此更适合于糖尿病相关疾病和代谢综合征的研究。PreClinOmics （PCO）已经开始开发一种新的没有瘦素/瘦素受体缺陷的大鼠模型，通过将选择的具有糖尿病倾向的大鼠模型与具有肥胖倾向的模型杂交。该项目的长期目标是创建一个大鼠模型，该模型将被生物技术和制药行业以及研究界所接受，以推进人类II型糖尿病治疗的研究和开发。该项目的第一阶段将集中于新的糖尿病大鼠模型的持续发展，定义和表征。这个项目有三个具体目标。首先，继续培养肥胖型糖尿病菌株，以及肥胖型非糖尿病菌株。其次，在肥胖-糖尿病大鼠模型中测试饮食操纵对表型表达（II型糖尿病）的发病和一致性的影响。第三，在该模型中研究一种典型的抗糖尿病化合物对糖尿病的预防作用，证明该模型对抗糖尿病化合物的反应能力的价值。项目描述：目前用于肥胖和糖尿病研究和药物开发的商业动物模型存在导致肥胖的遗传缺陷。这些缺陷在典型的肥胖和糖尿病个体中没有发现，在这些个体中，多基因似乎是导致这种情况的原因。本项目的目的是开发和生产一种新的多基因肥胖发展为糖尿病的动物模型。这应该是开发控制肥胖和成人发病糖尿病的药物的一个非常重要的模型。

DESCRIPTION (provided by applicant): Project Summary/Abstract: An estimated 18.2 million people (6.3 percent of the population) in the United States have diabetes; 90 to 95% of all diagnosed cases are type II diabetes (NIDDK, 2005). The search for new and more effective therapies to address the growing number of Americans with type II diabetes and related conditions is currently hindered by the lack of a research animal model that closely resembles the human diabetic condition. All rat models currently available commercially, related to metabolic syndrome and overt type II diabetes, have a genetic defect in leptin-receptor. On the contrary, leptin and leptin-receptor defects are not common causes for the etiology of obesity and diabetes in the human population. A rat model without this defect would more closely resemble the human condition and thus be more appropriate for the study of diabetic-related conditions and metabolic syndrome. PreClinOmics (PCO) has begun to develop a new rat model without leptin/leptin-receptor defects by crossing a selected rat model with the propensity to develop diabetes with a model that has the propensity to develop obesity. The long-term goal of this project is to create a rat model that will be accepted by biotech and pharmaceutical industries, and the research community to advance the study and development of type II diabetic therapies in humans. Phase I of the project will focus on the continued development, defining, and characterization of the new diabetic rat model. This project has 3 specific aims. First, continue to develop obese-diabetic strains, as well as an obese non-diabetic strain. Second, test the effects of diet manipulation on the onset and consistency of the phenotypic expression (type II diabetes) in the obese-diabetic rat model. Third, study the effects of a typical anti-diabetic compound on the prevention of diabetes in this model to demonstrate the value of the model in its ability to respond to anti-diabetic compounds. Project Narrative: Current commercially available animal models that are used for obesity and diabetes research and drug development have genetic defects that cause obesity. These defects are not found in the typical obese and diabetic individuals where polygenetic genes seem to be responsible for the condition. The purpose of this project is to develop and produce a new animal model that has polygenetic obesity which develops into diabetes. This should be a very important model to develop drugs that will control obesity and adult onset diabetes.