This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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