QUANTITATION OF FACTORS REGULATING GLUCOSE TOLERANCE

2型糖尿病是一种复杂的疾病，由慢性病引起。 糖耐量降低的进展，随后是高血糖。 了解复杂的变化模式是很有意义的。 在明显高血糖之前的代谢功能方面。三 导致糖耐量异常的成分是胰岛素。 抵抗力降低，B细胞功能受损，葡萄糖有效性降低。 后一个过程是葡萄糖本身增强的能力。 碳水化合物的处理和抑制内源性葡萄糖的输出。我们有 获得的数据支持这样一个概念，即在正常人中，B细胞 功能增强以补偿由以下原因引起的胰岛素抵抗 遗传或环境因素。事实上，数学乘积 胰岛素敏感性和胰岛素分泌之间的关系大致是恒定的。 造成这一双曲线关系的机制 在这项建议中，胰岛素敏感性和胰岛素分泌被研究。 糖耐量和B细胞反应变化的时间进程将 被监测，以澄清导致双曲线的事件 相互作用，并确定血液中负责的信号 这段令人震惊的关系。是否类似，但效率较低 当B细胞功能为 受损者将接受检查。此外，我们还将研究以下内容的重要性 个体代谢过程对葡萄糖的有效性有影响。的作用 肝脏或肾脏产生的葡萄糖，以及 将对胰岛素非依赖性和胰岛素依赖性组织进行评估。 还将考察在功能上发生的变化 当葡萄糖的有效性发生变化时，个别组织会发生变化。这些研究 应提供完整的手段的完整图景 生物体在小的时候维持正常的糖耐量 B细胞功能的改变是强加的，很可能提供新的 对类风湿关节炎发病机制和潜在治疗靶点的认识 2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.