QUANTITATION OF FACTORS REGULATING GLUCOSE TOLERANCE

2型糖尿病是一种复杂的疾病， 葡萄糖耐量降低的进展，随后是高血糖症。 了解变化的复杂模式是非常有意义的 在明显高血糖症之前代谢功能中。 三 导致葡萄糖耐受不良的成分是胰岛素 抵抗，受损的B细胞功能，和降低葡萄糖的有效性。 后一个过程是葡萄糖本身的能力增强 碳水化合物处置和抑制内源性葡萄糖输出。 我们有 获得的数据支持的概念，在正常人的B细胞 功能增加，以补偿胰岛素抵抗引起的 遗传或环境因素。 实际上， 胰岛素敏感性和胰岛素分泌的变化是大致恒定的。 负责双曲线关系的机制， 在该提议中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 监测以阐明解释双曲线的事件 相互作用，并确定血液中的信号， 这段惊人的关系 是否有类似的，但效率较低的 当B细胞功能被 受损的将被检查。 此外，我们还将研究 个体代谢过程对葡萄糖有效性的影响。 的作用 肝脏或肾脏产生葡萄糖，以及 将评估胰岛素非依赖性和胰岛素依赖性组织。 还将审查的变化发生的功能 当葡萄糖有效性改变时，个体组织。 这些研究 应提供一个完整的图片的手段， 当小的时候，机体维持正常的糖耐量 B细胞功能的改变是强加的，并且可以很好地提供新的 深入了解型糖尿病的发病机制和潜在的治疗靶点 2型糖尿病和糖尿病前期状态。

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.