MOLECULAR MAPPING OF NIDDM LOCI IN RODENTS AND HUMANS

啮齿动物和人类 NIDDM 位点的分子图谱

• 批准号: 2147104
• 负责人: STREAMSON C CHUA
• 金额: $ 27.52万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2147104
• 关键词: diabetes mellitus genetics; disease /disorder model; disease /disorder proneness /risk; family genetics; gene expression; genetic library; genetic markers; human genetic material tag; laboratory mouse; laboratory rat; linkage mapping; noninsulin dependent diabetes mellitus; obesity; polymerase chain reaction; diabetes mellitus genetics; disease /disorder model; disease /disorder proneness /risk; family genetics; gene expression; genetic library; genetic markers; human genetic material tag; laboratory mouse; laboratory rat; linkage mapping; noninsulin dependent diabetes mellitus; obesity; polymerase chain reaction

Type II or non-insulin dependent diabetes mellitus (NIDDM) is estimated to affect 5% of the world's population. Considering the additional 10-11% of the adult population with impaired glucose tolerance (which imposes a greater than 6-fold increased risk of developing NIDDM), 8-10% of adults either have, or will develop, NIDDM. Approximately 20% of the members of the US population over 65 years of age are diabetic. The medical consequences of this disorder are staggering. The complication rates in NIDDM patients are equivalent (per year of disease) to the much smaller number of individuals with type I, insulin-dependent diabetes. Diabetes is the leading cause of blindness, end stage renal disease and amputations in the US, and contributes significantly to the high prevalence of dyslipidemias and hypertension. The enormous physical and psychological burdens imposed by this disease are only partly reflected in the estimated $25 billion dollars spent annually on its treatment in the US alone. There is a strong genetic predisposition to NIDDM, the expression of which is facilitated by the presence of obesity. Over 60% of individuals with NIDDM are obese. The mechanisms by which obesity predisposes to NIDDM is not known, but it is likely that obesity stresses the pancreatic beta cells by diminishing the action of insulin on glucose metabolism. The goal of this proposal is to identify the genes which, in the presence of obesity, predispose to the development of NIDDM. The complexity of the genetics of NIDDM in humans favors the initial use of simpler animals models to identify candidate genes for NIDDM- susceptibility and resistance. Using well characterized mouse and rat genetic models of obesity-diabetes, such genes will be identified. These genes will be then be examined by genetic linkage techniques in human families in which NIDDM is present. Ultimately, knowledge of the structure/action of such genes can be used to prevent or treat NIDDM.

II型或非胰岛素依赖性糖尿病（NIDDM）估计为 影响5％的世界人口。考虑到额外的10-11％ 葡萄糖耐受性受损的成年人口 大于6倍的NIDDM风险增加），成年人中有8-10％ 要么有或将发展为NIDDM。大约20％的成员 美国65岁以上的美国人口是糖尿病患者。 这种疾病的医疗后果令人震惊。并发症 NIDDM患者的率是同等的（每年疾病） I型，胰岛素依赖性糖尿病的个体较少。 糖尿病是失明，末期肾脏疾病和 在美国的截肢，并为高 血脂异常和高血压的患病率。巨大的身体和 这种疾病施加的心理负担仅部分反映在 估计每年在其治疗上花费了大约250亿美元 我们一个人。 NIDDM有强烈的遗传易感性，其表达 肥胖的存在促进了。超过60％的人 NIDDM肥胖。肥胖症易于NIDDM的机制为 尚不清楚，但肥胖很可能会强调胰腺β 通过减少胰岛素对葡萄糖代谢的作用来减少细胞。目标 该提议的内容是确定在存在下的基因 肥胖，易于发展NIDDM的发展。 NIDDM在人类中的遗传学的复杂性有利于初始用途 较简单的动物模型，以鉴定NIDDM-的候选基因 敏感性和抵抗力。使用良好的鼠标和大鼠 将鉴定出肥胖 - 糖尿病的遗传模型。这些 然后将通过人类的遗传连锁技术来检查基因 存在NIDDM的家庭。最终，了解 这种基因的结构/作用可用于预防或治疗NIDDM。