STUDIES IN GLUCOSE HOMEOSTASIS

血糖浓度通常维持在一个狭窄的范围内。 由一组协调的生理过程组成， 自我平衡系统 体内平衡调节的异常可能 占大多数临床糖代谢紊乱，最常见的 即糖尿病。 参与遗传因素的研究 葡萄糖稳态主要集中在定量遗传学上， 分析异常表型，通常是糖尿病。 多方面的结果 工作提供了几乎部分的洞察力，遗传因素的重要性， 糖尿病的病因和发病机制;低血糖已收到远 更少的关注。 我们假设，以前工作的一个主要问题是， 不适当地关注表型，即糖尿病，这可能是 远离相关的致病基因，难以定义， 年龄依赖性。 我们已经开发了动态平衡的数学模型;特别是， 测量特性对扰动的响应已被研究， 到扰动力和时间之间的滞后时间（L）， 恢复力反作用，以及该力的强度（B）。 我们推测 正是这些特征，特别是滞后时间， 控制 我们已经证明，在理论上，延迟时间的延长 一定会导致韵律的偏差（甚至是无法控制的偏差） 性状（如血糖）从一个狭窄的变化范围到一个 更高的范围。 我们建议研究先证者及其近亲， 确定滞后时间（根据葡萄糖耐量试验数据计算） 同意对胰岛素和胰高血糖素血液水平的直接研究，以及如何 它是遗传的。 先证者将从个体中选择（1） 无血糖紊乱的临床证据，（2）新发 诊断为患有II型糖尿病，（3）患有 青年（MODY），和（4）与各种孟德尔疾病，为 不同的原因，导致葡萄糖稳态异常。

The blood glucose concentration is ordinarily maintained within a narrow range by a coordinated set of physiologic processes that collectively form a homeostatic system. Abnormalities of homeostatic regulation probably account for most clinical disorders of glucose metabolism, the most common being diabetes mellitus. Investigations of genetic factors involved in glucose homeostasis have focused, by and large, on quantitative genetic analysis of abnormal phenotypes, generally diabetes. The results of much work provide barely partial insight to the genetic factors important in the etiology and the pathogenesis of diabetes; hypoglycemia has received far less attention. We suppose that one major problem with previous work has been improper focus on phenotype, that is diabetes, which is probably remote from the etiological genes concerned, difficult to define, and age-dependent. We have developed mathematical models of homeostasis; in particular, the response of a metrical trait to perturbation has been studied with respect to the lag time (L) between a perturbing force and the time at which restorative forces react, and the strength of that force (b). We speculate that it is these features, especially the lag time, that are under genetic control. We have demonstrated how, in theory, prolongation of the lag time must result in deviation (even uncontrollable deviation) of the metrical trait (such as blood glucose) from one narrow range of variation to a higher range. We propose studying probands and their close relatives to determine how the lag time (calculated from glucose tolerance test data) agrees with direct studies on blood levels of insulin and glucagon, and how it is inherited. Probands will be selected from among individuals (1) without clinical evidence of disorders of blood glucose, (2) newly diagnosed as having type II diabetes, (3) with maturity-onset diabetes of youth (MODY), and (4) with a variety of mendelian disorders that, for different reasons, result in abnormal glucose homeostasis.