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. Recent evidence from animal studies in our lab suggests that insulin has two distinct vascular actions in skeletal muscle. One is to increase total blood flow the second is the recruitment of new capillaries which thereby enhance the perfusion of muscle. We have recently performed human insulin clamp studies and insulin appears to have the same effect on blood flow and capillary recruitment in human skeletal muscle. More recently we have examined the effect of a mixed meal challenge in healthy young adults. We observed that even this transitory increase in plasma insulin concentration was associated with a significant increase in skeletal muscle microvascular perfusion. Based upon studies we have performed in animals where inhibition of microvascular recruitment using a nitric oxide synthase inhibitor is observed to also inhibit skeletal muscle glucose uptake, we believe that the microvascular effect of insulin may be critical to overall insulin-mediated glucose disposal. The purpose if the present study is to look at the effect of a mixed meal challenge on forearm blood flow and microvascular perfusion in persons with the 'insulin-resistance' syndrome secondary to either obesity, hypertension, or type 2 diabetes.
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