MECHANISMS OF GROWTH HORMONE HYPERSECRETION IN DIABETES

我的目标是调查与糖尿病和激素相关的领域 糖尿病并发症的发病机制。 实验 旨在阐明生长分泌过多的机制， 将在Dr. L. 弗罗曼 （a）脑垂体的作用 生长抑素抵抗（SRIH）在糖尿病GH分泌过多中的作用 生长激素释放的剂量-反应关系 激素（GRH）诱导的GH分泌在一系列分级SRIH的每一个 将在正常受试者和I型糖尿病患者之间比较输注 在严格控制血糖之前和之后 (b)的影响 糖尿病对生长激素分泌昼夜节律的具体特点 将评估（基线浓度vs峰值振幅和频率） 以确定它们是否涉及控制权的具体变更 机制等 (c)细胞内葡萄糖减少被认为是介导生长激素 对血糖的反应。 葡萄糖与生长激素分泌的关系 正常和糖尿病大鼠将在诱导损伤后测定， 已知介导下丘脑视交叉上核 对2-脱氧葡萄糖诱导的细胞内葡萄糖减少的反应。 这将 建立一个单一的机制是否可以解释急性GS反应 和GH对糖尿病的慢性适应 或者是否需要多个机制。 (d)为了解决的作用 糖尿病GH异常时GRH分泌改变， 将开发超灵敏的GRH免疫测定法。 这项技术将使用 一种物理标记，细菌酶荧光素酶， 与RIA相比提高了灵敏度。 长期以来，人们一直认为糖尿病患者GH分泌异常， 所涉及的机制尚不清楚。 在严格控制血糖的同时 使血浆GH浓度正常化，这种控制目前还不能 在大多数I型糖尿病患者中维持很长时间。 从目前的调查中获得的信息应证明是有用的， 确定GH抑制是否有助于改善血糖控制 以及评估GH在糖尿病视网膜病变发展中的作用， 与儿童期糖尿病相关的生长障碍。 这也可能证明 用于计划和评估治疗方案的安全性， 非糖尿病儿童生长障碍中的生物合成GH。

My goal is to investigate areas related to diabetes mellitus and hormonal mechanisms in the pathogenesis of complications of diabetes. Experiments designed to elucidate mechanisms underlying the hypersecretion of growth hormone (GH) in diabetes will be performed under the sponsorship of Dr. L. Frohman. The questions to be addressed are: (a) The role of pituitary resistance to somatostatin (SRIH) in hypersecretion of GH in diabetes. Dose-response relationships for growth hormone releasing hormone(GRH)-induced GH secretion during each of a series of graded SRIH infusions will be compared between normal subjects and type I diabetics before and after instituting tight glycemic control. (b) The effect of diabetes on specific features of the diurnal rhythm of GH secretion (baseline concentration vs peak amplitude and frequency) will be assessed to determine whether they implicate specific alterations in control mechanisms. (c) Intracellular glucopenia is thought to mediate the GH response to plasma glucose. The relationship of GH secretion to glucose in normal and diabetic rats will be determined after induction of lesions in the hypothalamic suprachiasmatic nuclei which are known to mediate responses to intracellular glucopenia induced by 2-deoxyglucose. This will establish whether a single mechanism can explain both the acute GS response to glucose and the seemingly opposite chronic adaptation of GH to diabetes or whether multiple mechanisms are required. (d) To address the role of altered secretion of GRH in GH abnormalities in diabetes, an ultra-sensitive GRH immunoassay will be developed. This technique will use a physical marker, the bacterial enzyme luciferase, that should markedly improve sensitivity over that achieved with RIA. Abnormalities in GH secretion in diabetes have long been recognized but the mechanisms involved are not understood. While tight glycemic control normalizes the plasma GH concentration, such control is presently not maintained for long periods in most people with type I diabetes. Information gained from the present investigation should prove useful in determining whether GH suppression will aid in improving glycemic control and in evaluating GH's role in the development of diabetic retinopathy and growth disorders associated with diabetes in childhood. It may also prove useful in planning and evaluating the safety of treatment regimens for biosynthetic GH in growth disorders in non-diabetic children.