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INSULIN-ADENOSINE RELATIONSHIPS AND INSULIN ACTION

胰岛素-腺苷关系和胰岛素作用

基本信息

批准号：
3446002
负责人：
THEODORE P. CIARALDI
金额：
$ 4.15万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-08-01 至 1986-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446002
关键词：
adenine analog adenosine adipocytes adrenalectomy basal metabolism glucose transport high performance liquid chromatography insulin insulinlike factor liver cells

项目摘要

In addition to its own effects, adenosine is known to augment some of insulin's actions on intermediary metabolism in adipose tissue. This study will probe the relationship between insulin and adenosine in isolated adipocytes and hepatocytes and the ability of adenosine to alter the coupling of insulin binding to stimulation of glucose transport and protein synthesis. First to be studied will be the ability of changes in adenosine levels (by enzymatic destruction and/or replacement with nonmetabolizable analogs) to alter the characteristics of insulin binding in the two cell types. Direct effects of adenosine on glucose transport and protein synthesis will be tested as well as its ability to influence stimulation of these two responses by insulin and insulin mimickers. These data will reveal if adenosine influences insulin action by altering binding, having a direct effect on the responsive systems (possibly due to a role as a second messenger), or by acting to control the efficiency of coupling between occupied insulin receptors and responses. The effects of insulin treatment on several aspects of adenosine metabolism: release from cells, transport, and specific receptor binding, will also be tested. Many of these studies will be performed in cells prepared from adrenalectomized rats to localize the pertubation that is responsible for the adenosine dependent changes in insulin sensitivity with adrenal insufficiency. Glucose transport and protein synthesis will be studied for they differ in the time course of their responses as well as the mechanisms by which insulin alters these activities. Adipocytes and hepatocytes will be compared for they differ in their responses to adenosine. They also are different in that while protein synthesis is stimulated by insulin in both cell types, glucose transport is insulin responsive only in adipocytes. Differences in the handling of adenosine may account for the variation in glucose transport responsiveness to insulin. It is hoped that by looking at how adenosine alters coupling this project will aid understanding of the mechanisms of insulin-effector system coupling and how this coupling process may be subjected to physiological control.

除了其自身的作用外，已知腺苷还可以增加一些胰岛素在脂肪组织中间代谢中的作用。本研究将探讨胰岛素和腺苷之间的关系，脂肪细胞和肝细胞和腺苷的能力，以改变胰岛素结合与葡萄糖转运和蛋白质刺激的偶联合成. 首先要研究的将是腺苷变化的能力，水平（通过酶促破坏和/或用非代谢物替代类似物）以改变两个细胞中胰岛素结合的特征类型腺苷对葡萄糖转运和蛋白质的直接作用将测试合成以及其影响刺激的能力，胰岛素和胰岛素模拟物的这两种反应。这些数据将揭示腺苷是否通过改变结合来影响胰岛素作用，对响应系统的直接影响（可能是由于作为第二个信使），或通过作用来控制耦合之间的效率，占据胰岛素受体和反应。胰岛素治疗的效果腺苷代谢的几个方面：从细胞释放，运输，和特异性受体结合也将被测试。许多这些研究将在肾上腺切除大鼠制备的细胞中进行定位引起腺苷依赖性变化的扰动，胰岛素敏感性伴肾上腺功能不全葡萄糖转运和蛋白质合成将被研究，因为它们在时间过程中不同，它们的反应以及胰岛素改变这些反应的机制活动将比较脂肪细胞和肝细胞，因为它们在对腺苷的反应他们也是不同的，在两种细胞类型中，蛋白质合成都受到胰岛素的刺激，葡萄糖转运仅在脂肪细胞中是胰岛素响应性的。差异腺苷的处理可以解释葡萄糖转运的变化对胰岛素的反应。希望通过观察腺苷改变耦合这个项目将有助于了解的机制，胰岛素-效应子系统偶联以及该偶联过程如何受到生理控制。