MECHANISMS OF GROWTH HORMONE HYPERSECRETION IN DIABETES

我的目标是研究与糖尿病和荷尔蒙相关的领域 糖尿病并发症发病机制的研究。实验 旨在阐明生长过度分泌的潜在机制 糖尿病的激素(GH)将在L博士的赞助下进行。 弗罗曼。需要解决的问题是：(A)脑下垂体的作用 糖尿病患者生长激素高分泌对生长抑素的抵抗 生长激素释放的剂量-反应关系 激素(GRH)在一系列分级的SRIH中诱导的GH分泌 将比较正常受试者和I型糖尿病患者的输液情况 在制定严格的血糖控制措施前后。(B) 糖尿病患者生长激素分泌昼夜节律的特点 (基线浓度与峰值幅度和频率)将进行评估 以确定它们是否涉及控制中的特定变化 机械装置。(C)细胞内糖减少症被认为是GH的中介 对血糖的反应。大鼠生长激素分泌与血糖的关系 正常大鼠和糖尿病大鼠将在诱发病变后确定 下丘脑视交叉上核团是已知的 对2-脱氧葡萄糖引起的细胞内糖减少症的反应。这将是 确定单一机制是否可以解释急性GS反应 对葡萄糖和看似相反的生长激素对糖尿病的慢性适应 或者是否需要多种机制。(D)解决以下问题： 糖尿病患者GH异常的GRH分泌改变及 将开发超灵敏的GRH免疫分析方法。这项技术将使用 一种物理标记，细菌酶荧光素酶，应该显著 与RIA相比，提高了灵敏度。 糖尿病患者的生长激素分泌异常早已被认识到，但 其中涉及的机制尚不清楚。严格控制血糖的同时 使血浆生长激素浓度正常化，目前还没有这样的控制 在大多数I型糖尿病患者中维持较长时间。 从目前的调查中获得的信息应被证明对 确定抑制生长激素是否有助于改善血糖控制 在评估生长激素在糖尿病视网膜病变的发生和发展中的作用 儿童时期与糖尿病相关的生长障碍。这也可能证明 有助于规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生长激素。

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.