INSULIN MEDIATED FOREARM MUSCLE MICROVASCULAR RECRUITMENT AND INSULIN UPTAKE

胰岛素介导的前臂肌肉微血管募集和胰岛素摄取

• 批准号: 8167157
• 负责人: EUGENE Joseph BARRETT
• 金额: $ 4.54万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167157
• 关键词: Address; Area Under Curve; Blood Vessels; Blood capillaries; Computer Retrieval of Information on Scientific Projects Database; Exercise; Fat emulsion; Forearm; Frequencies; Funding; Glucose; Grant; Human; Hyperinsulinism; Infusion procedures; Institution; Insulin; Measurement; Measures; Mediating; Muscle; Muscle Contraction; Nonesterified Fatty Acids; Physiological; Plasma; Protocols documentation; Research; Research Personnel; Resources; Rodent; Skeletal Muscle; Source; Testing; Time; Ultrasonography; United States National Institutes of Health; Venous; basal insulin; capillary; glucose uptake; uptake

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. The hypothesis of this protocol posits that insulin-mediated muscle microvascular recruitment in healthy humans occurs early and this microvascular recruitment facilitates insulin delivery to skeletal muscle. To test this hypothesis, we will directly measure: 1) insulin extraction (arterial-venous concentration) and absolute flux ((A-V) x Flow) by human forearm skeletal muscle, and 2)the extent of microvascular recruitment as assessed by contrast enhanced ultrasound (CEU). Measurements will be made basally and during steady-state hyperinsulinemia in two groups: subjects in whom insulin uptake and insulin-induced microvascular recruitment occur in a normal physiologic setting, and those in whom insulin-induced microvascular recruitment is blocked by the co-infusion of Intralipid to raise plasma free fatty acids (FFA). Intralipid has been shown to block insulin-mediated capillary recruitment in rodents. Finally, we will examine whether modest intensity, low-frequency muscle contraction stimulates insulin and glucose uptake by forearm muscle and conditions of basal insulin. Primary endpoints are the rate of insulin and glucose uptake by forearm muscle during insulin infusion and during low-frequency exercise and the difference in microvascular volume between groups. Comparisons will be made by a 2-way repeated measures ANOVA with effects of time and treatment. For the primary comparison of muscle insulin and glucose uptake, we will integrate the area under the curve to determine differences in total cumulative glucose and insulin uptake during the course of the study. We will also estimate the T1/2 and the absolute delta for changes in microvascular volume versus insulin and glucose uptake to address both the temporal and dimensional relationships between vascular recruitment and insulin uptake by muscle.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该协议的假设认为，健康人体中胰岛素介导的肌肉微血管募集发生得很早，并且这种微血管募集促进胰岛素输送到骨骼肌。为了检验这一假设，我们将直接测量：1）人类前臂骨骼肌的胰岛素提取量（动静脉浓度）和绝对流量（（A-V）x流量），以及2）通过对比增强超声评估的微血管募集程度（中欧大学）。将在基础上和稳态高胰岛素血症期间对两组进行测量：在正常生理环境下发生胰岛素摄取和胰岛素诱导的微血管募集的受试者，以及在共同输注胰岛素诱导的微血管募集被阻断的受试者中。 Intralipid 可提高血浆游离脂肪酸 (FFA)。脂肪乳已被证明可以阻止啮齿类动物胰岛素介导的毛细血管募集。最后，我们将检查适度强度、低频的肌肉收缩是否会刺激前臂肌肉对胰岛素和葡萄糖的摄取以及基础胰岛素的条件。主要终点是胰岛素输注和低频运动期间前臂肌肉的胰岛素和葡萄糖摄取率以及组间微血管体积的差异。将通过 2 路重复测量方差分析对时间和治疗的影响进行比较。为了对肌肉胰岛素和葡萄糖摄取进行初步比较，我们将积分曲线下面积，以确定研究过程中总累积葡萄糖和胰岛素摄取的差异。 我们还将估计 T1/2 和微血管体积相对于胰岛素和葡萄糖摄取变化的绝对增量，以解决血管募集和肌肉胰岛素摄取之间的时间和维度关系。