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Role of Insulin Biosynthesis in Glucose Tolerance

胰岛素生物合成在葡萄糖耐量中的作用

基本信息

批准号：
9135791
负责人：
DANIEL T STEIN
金额：
$ 2.96万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9135791
关键词：
Role Insulin Biosynthesis Glucose Tolerance

项目摘要

The ultimate goal of this proposal is to determine the cause(s) of impaired glucose tolerance leading to type 2 diabetes. An improved understanding of the underlying pathophysiology of the early events should provide a rational basis for the development of improved methods of early diagnosis and ultimately treatments for type 2 diabetes. The pancreatic beta cell response to nutrient oversupply and obesity associated insulin resistance is compensatory insulin hypersecretion in order to maintain euglycemia. Diabetes, and early states of glucose intolerance only develop in those who develop beta cell dysfunction. Although beta cell mass has been found to decline by ~50% in those with prediabetic states of glucose intolerance, controversy exists as to whether defects in the beta cell secretory response is due to deficient synthetic machinery or functional defects in glucose sensing and insulin secretion. This proposal will test the hypothesis that intrinsic or acquired defects in insulin biosynthesis characterize states of glucose intolerance, that these defects result in depletion of a rapidly mobilizable pool of insulin necessary for fully efficient beta cell function in response to nutrient stimuli. Insulin biosynthetic rates and relative sizes of intracellular beta cell pools will be measured for the first time in vivo in streptozotocin treated rats, and in subjects with normal, impaired glucose tolerance and diabetes by the novel method of mass isotopomer distribution analysis.

这项建议的最终目的是确定血糖受损的原因(S) 耐受性导致2型糖尿病。更好地理解潜在的早期事件的病理生理学应为其发展提供合理的依据改进了2型糖尿病的早期诊断和最终治疗方法。胰岛β细胞对营养过剩和肥胖相关胰岛素的反应抵抗是为了维持正常血糖而进行的代偿性胰岛素高分泌。糖尿病和早期状态的葡萄糖不耐受只在那些发展成 β细胞功能障碍。尽管贝塔细胞质量已被发现在对于那些有糖尿病前期状态的人来说，是否存在争议 β细胞分泌反应的缺陷是由于合成机械或血糖感知和胰岛素分泌的功能缺陷。这项提案将考验胰岛素生物合成中固有或后天缺陷表征状态的假说这些缺陷会导致快速动员池的耗尽对营养刺激作出反应的完全有效的β细胞功能所需的胰岛素。胰岛素生物合成率和细胞内β细胞池的相对大小将是首次在链脲佐菌素处理的大鼠和用新质量法研究糖耐量正常、糖耐量受损与糖尿病同分异构体分布分析。