INSULIN'S ACTION ON CAPILLARY RECRUITMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议集中在胰岛素S对胰岛素抵抗的非糖尿病亚裔印度人的整体和微血管血流灌注的作用，以及它们与葡萄糖代谢的关系。这个项目的主要目标是评估生理水平的胰岛素是否通过使用对比增强超声技术通过毛细血管再充盈来增强人体骨骼肌中的微血管灌注量。我们期望看到S胰岛素对毛细血管募集和总血流量作用的分离。具体地说，我们假设S胰岛素对毛细血管募集的作用早于血流的改变，并且毛细血管募集与S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裔印度人是否钝化了毛细血管募集，这与他们胰岛素敏感性降低有关。体重指数和年龄匹配的健康亚裔印度人和高加索人将接受高胰岛素正血糖钳夹治疗，并在基线和高胰岛素血症30分钟和120分钟后测量毛细血管复张和臂动脉血流量，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在其增加总血流量的作用发生之前增加毛细血管的募集和葡萄糖的摄取。我们假设，与高加索人相比，胰岛素抵抗的亚裔印度人将会有毛细血管重新募集的钝化，并且钝化的程度与骨骼肌对葡萄糖摄取的减少之间将存在显著的相关性。

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.