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.The central focus of this study has been on the importance of resistance to insulin-mediated glucose disposal and compensatory hyperinsulinemia in modulation of metabolic changes that increase risk of coronary heart disease (CHD). These can include more obvious well-known CHD risk factors, such as dyslipidemia and hypertension and others leading to the cluster of abnormalities known as Syndrome X. Besides focusing on these risk factors, we will also evaluate changes in endothelium-dependent vasodilation (endothelium-dependent vascular reactivity, EDVR) and determinants of endothelial-monocyte interaction that comprise the earliest steps in atherogenesis. Therefore, we will be attempting to establish a link between insulin resistance and the cluster of metabolic abnormalities associated with this defect in insulin action. We will also try and establish the link with insulin resistance and endothelium-dependent vasodilatation and determinants of endothelium-monocyte interaction.
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