INSULIN'S ACTION ON CAPILLARY RECRUITMENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项建议的重点是胰岛素的行动散装和微血管灌注，以及它们与葡萄糖代谢的胰岛素抵抗非糖尿病亚洲印度人。本项目的主要目标是评估生理水平的胰岛素是否通过毛细血管募集增强人体骨骼肌中的微血管灌注，使用超声造影技术。我们希望看到胰岛素对毛细血管募集和总血流量的作用之间的分离。具体而言，我们假设胰岛素对毛细血管募集的作用早于血流变化，并且毛细血管募集与胰岛素刺激骨骼肌葡萄糖摄取的能力之间存在直接关系。我们的第二个目标是确定健康的亚洲印度人是否有与胰岛素敏感性降低相关的毛细血管募集减弱。BMI和年龄匹配的健康亚洲印度人和高加索人将接受高胰岛素正葡萄糖钳夹试验，并在基线时以及高胰岛素血症30分钟和120分钟后测量毛细血管募集和肱动脉血流量，以评估血管反应性和葡萄糖摄取之间的时间关系。我们预计，生理剂量的胰岛素将增加毛细血管募集和葡萄糖摄取之前，其增加总血流量的影响发生。我们假设，胰岛素抵抗的亚洲印度人将有钝化的毛细血管募集，并将有一个显着的相关性之间的程度钝化和减少葡萄糖摄取的骨骼肌相比，高加索人。

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. This proposal focuses on insulin's action on both bulk and microvascular perfusion, and their relation to glucose metabolism in insulin resistant non-diabetic Asian Indians. The primary goal of this project is to assess if physiological levels of insulin enhance microvascular perfusion in human skeletal muscle by capillary recruitment, using the technique of contrast-enhanced ultrasound. We expect to see dissociation between insulin's action on capillary recruitment and total blood flow. Specifically, we hypothesize that insulin's action on capillary recruitment occurs earlier than changes in blood flow, and that there is a direct relationship between capillary recruitment and insulin's ability to stimulate glucose uptake in the skeletal muscle. Our second goal is to determine if healthy Asian Indians have blunted capillary recruitment that is related to their decreased insulin sensitivity. Healthy Asian Indian and Caucasians matched for BMI and age will undergo a hyperinsulinemic euglycemic clamp, and will have capillary recruitment and brachial artery blood flow measured at baseline, and after 30 and 120 minutes of hyperinsulinemia to assess the temporal relationship between vascular reactivity and glucose uptake. We anticipate that physiological doses of insulin will increase capillary recruitment and glucose uptake before its effect on increasing total blood flow occurs. We hypothesize that insulin resistant Asian Indians will have blunting of capillary recruitment, and that there will be a significant correlation between the magnitude of the blunting and the reduction in glucose uptake by the skeletal muscle compared to Caucasians.