AIM 8: MAINTENANCE OF THE POSTABSORPTIVE PLASMA GLUCOSE CONCENTRATION

目标 8：维持吸收后血浆葡萄糖浓度

• 批准号: 7377223
• 负责人: PHILIP E. CRYER
• 金额: $ 3.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377223
• 关键词: AIM; MAINTENANCE; POSTABSORPTIVE; PLASMA; GLUCOSE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Increments in glucagon, in concert with decrements in insulin, play a key role in the prevention, as well as the correction, of clinical (i.e., symptomatic) hypoglycemia when plasma glucose concetration fall below the physiological range. The role of glucagon in maintenance of the postabsorptive plasma glucose concentration within the physiological range is less clear-cut. The prevalent view is that the postabsorptive plasma glucose concentration is maintained within the physiological range (70 to 110 mg/dL in humans) by the interplay of the glucose-lowering action of insulin and the glucose-raising action of glucagon. However, as detailes in the attached protocol, much of the evidence that seemingly supports that view, including our own, is open to alternative interpretations. Therfore, we plan to re-examine this issue - by testing the hypothesis that glucagon does not support the postabsorptive plasma glucose concentration in healthy humans - using the islet clamp technique, somatostatin (octreotide) infusion to suppress endogenous insulin and glucagon (and growth hormone) secretion alone, with insulin replacement, with glucagon replacement. We plan to first critically assess the components of the islet clamp technique and then to use it to test our hypothesis. In Aim 8.1 we will determine the glycemic effects, if any, and the plasma concentrations of the hormone doses selected (from the literature, from our experience and in view of our hypothesis) for basal replacement during islet clamps in healthy humans. Then, in Aim 8.2, we expect to confirm the glycemic responses to somastatin (here with the somatostatin analogue octreotide) alone and with insulin replacement and test our hypothesis further by also replacing glucagon and insulin plus glucagon. While the prevalent view may be correct, we believe that the alternative view that the postabsorptive plasma glucose concentration is maintained within the physiological range by insulin alone is plausible and, therefore, that this issue needs more definitive evidence in humans.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。当血浆葡萄糖浓度低于生理范围时，胰高血糖素的增加与胰岛素的减少相结合，在预防和纠正临床（即症状性）低血糖方面发挥着关键作用。胰高血糖素在将吸收后血浆葡萄糖浓度维持在生理范围内的作用尚不清楚。普遍的观点是，通过胰岛素降血糖作用和胰高血糖素升血糖作用的相互作用，吸收后血浆葡萄糖浓度维持在生理范围内（人类为70至110 mg/dL）。然而，正如所附协议中的详细信息，许多看似支持该观点的证据，包括我们自己的证据，都可以接受其他解释。因此，我们计划重新审视这个问题——通过检验胰高血糖素不支持健康人吸收后血浆葡萄糖浓度的假设——使用胰岛钳技术、生长抑素（奥曲肽）输注来抑制内源性胰岛素和胰高血糖素（以及生长激素） ）单独分泌，用胰岛素替代，用胰高血糖素替代。我们计划首先严格评估胰岛钳技术的组成部分，然后用它来检验我们的假设。在目标 8.1 中，我们将确定健康人胰岛钳夹期间基础替代的血糖影响（如果有）以及所选激素剂量的血浆浓度（来自文献、我们的经验并考虑到我们的假设）。然后，在目标 8.2 中，我们期望确认单独使用生长抑素（此处为生长抑素类似物奥曲肽）和胰岛素替代的血糖反应，并通过替代胰高血糖素和胰岛素加胰高血糖素进一步检验我们的假设。虽然普遍的观点可能是正确的，但我们认为，仅靠胰岛素将吸收后血浆葡萄糖浓度维持在生理范围内的另一种观点是合理的，因此，这个问题需要在人类中提供更明确的证据。