QUANTITATION OF FACTORS REGULATING GLUCOSE TOLERANCE

葡萄糖耐量调节因素的定量

• 批准号: 6128534
• 负责人: RICHARD Nathan BERGMAN
• 金额: $ 4.33万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128534
• 关键词: androgens; diet; dietary lipid; dogs; exercise; free fatty acids; glucose clamp technique; glucose metabolism; glucose tolerance; glucose transport; hormone therapy; hyperglycemia; injection /infusion; insulin; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; nutrition related tag; pancreatic islet function; pancreatic islets; somatotropin; troglitazone

Type 2 diabetes is a complex disease which is caused by a slow progression of decreased glucose tolerance, followed by hyperglycemia. it is of great interest to understand the complex patterns of changes in metabolic function which precede overt hyperglycemia. Three components which can contribute to glucose intolerance are insulin resistance, impaired B-cell function, and reduced glucose effectiveness. The latter process is the ability of glucose itself to enhance carbohydrate disposal and suppress endogenous glucose output. We have obtained data supporting the concept that in normal individuals B-cell function increases to compensate for insulin resistance caused by hereditary or environmental factors. In fact, the mathematical product of insulin sensitivity and insulin secretion is approximately constant. The mechanisms responsible for the hyperbolic relationship between insulin sensitivity and insulin secretion are studied in this proposal. The time course of changes in glucose tolerance and B-cell response will be monitored to elucidate the events which account for the hyperbolic interaction, and to identify the signals in blood which are responsible for this striking relationship. Whether a similar, but less efficient hyperbolic relationship can be maintained when B-cell function is impaired will be examined. Also, we will examine the importance of individual metabolic precesses to glucose effectiveness. The role of glucose production by liver or kidney, as well as glucose uptake by insulin independent and insulin dependent tissues will be assessed. Also examined will be the changes which take place in function of individual tissues when glucose effectiveness changes. These studies should provide an integrated picture of the means by which the intact organism maintains normal maintenance of glucose tolerance when small changes in B-cell function are imposed, and could well provide new insights into the pathogenesis and potential treatment targets for Type 2 diabetes and the prediabetic state.

2型糖尿病是一种复杂的疾病，是由于缓慢而引起的 葡萄糖耐受性降低的进展，其次是高血糖。 了解变化的复杂模式是非常有趣的 在明显高血糖之前的代谢功能中。 三 可能导致葡萄糖不耐症的成分是胰岛素 电阻，B细胞功能受损以及葡萄糖有效性降低。 后一个过程是葡萄糖本身增强的能力 碳水化合物处置并抑制内源性葡萄糖输出。 我们有 获得了支持正常个体B细胞的数据 功能增加以补偿由 遗传或环境因素。 实际上，数学产品 胰岛素敏感性和胰岛素分泌的分泌大约是恒定的。 导致双曲线关系的机制 该提案研究了胰岛素敏感性和胰岛素分泌。 葡萄糖耐量和B细胞反应变化的时间过程将 监视以阐明说明双曲线的事件 互动，并确定血液中负责的信号 对于这种惊人的关系。 是否类似但效率较低 当B细胞函数为 受损将被检查。 另外，我们将研究 单个代谢进攻型葡萄糖有效性。 的作用 肝脏或肾脏的葡萄糖产生，以及葡萄糖吸收 将评估胰岛素独立和胰岛素依赖性组织。 还将检查的是在功能中发生的更改 当葡萄糖有效性变化时，各个组织。 这些研究 应该提供完整的手段的综合图片 当小时 B细胞功能的变化被施加，并且很可能提供新的 对类型的发病机理和潜在治疗靶标的见解 2个糖尿病和糖尿病前期。