STUDIES IN GLUCOSE HOMEOSTASIS

血糖浓度通常维持在较低的范围内。 由一组协调的生理过程共同形成的范围 一个动态平衡系统。可能是体内平衡调节异常 临床上占多数的糖代谢紊乱，是最常见的 是糖尿病患者。有关遗传因素的研究进展 大体上，葡萄糖动态平衡主要集中在数量遗传上。 分析异常表型，一般为糖尿病。多年来的成果 工作仅仅提供了对遗传因素的部分洞察力 糖尿病的病因学和发病机制；低血糖 更少的关注。我们认为以前工作的一个主要问题是 一直不恰当地关注表型，那就是糖尿病，这可能是 远离相关的致病基因，难以定义，以及 依年龄而定。 我们已经开发了动态平衡的数学模型；特别是， 从以下方面研究了度量性状对扰动的响应 关于扰动力和时间之间的滞后时间(L) 恢复性力量的反应，以及这种力量的强度(B)。我们推测 正是这些特征，特别是滞后时间，是在基因 控制力。我们已经演示了，在理论上，如何延长滞后时间 必须导致测量的偏差(甚至无法控制的偏差) 性状(如血糖)从一个狭窄的变异范围到一个 更高的射程。我们建议研究先证者及其近亲 确定滞后时间(根据葡萄糖耐量测试数据计算) 同意对血液中胰岛素和胰升糖素水平的直接研究，以及如何 这是遗传的。先证者将从个人中挑选(1) 没有临床证据的血糖紊乱，(2)新 诊断为II型糖尿病，(3)成熟期糖尿病 青年(MODY)，和(4)有各种孟德尔障碍，对于 不同的原因，导致血糖稳态异常。

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.