This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
Name: Sildenafil Citrate
Description: phosphodiesterase 5 inhibitorType: DrugSildenafil citrate
Description: The primary endpoint is the change in microvascular blood volume (ΔMBV) during insulin infusion from baseline, an index of insulin-stimulated microvascular recruitment.
Measure: insulin-stimulated microvascular recruitment. Time: 4 weeksDescription: Glucose infusion rate during hyperinsulinemic euglycemic clamp
Measure: Insulin sensitivity Time: 4 weeksSingle Group Assignment
There is one SNP
CD36 in Nutrient Delivery and Its Dysfunction This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
- Hematocrit < 34% - Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult - Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) - History of alcohol or drug abuse - Treatment with any investigational drug in the one month preceding the study - Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study - Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and investigator discretion Insulin Resistance Endothelial Dysfunction Insulin Resistance Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in ~25% of African Americans have endothelial dysfunction.