CD36 in Nutrient Delivery and Its Dysfunction
Last updated on July 2021Recruitment
- Recruitment Status
- Active, not recruiting
- Estimated Enrollment
- 40
Summary
- Conditions
- Endothelial Dysfunction
- Insulin Resistance
- Type
- Interventional
- Phase
- Phase 1Phase 2
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Basic Science
Participation Requirements
- Age
- Between 18 years and 50 years
- Gender
- Both males and females
Description
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. Endothelial dysfunction results in impairment of insulin's vascular actions and eventually reduced insulin sensitivity. Insulin induces ...
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. Endothelial dysfunction results in impairment of insulin's vascular actions and eventually reduced insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle. Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month treatment with sildenafil improves insulin sensitivity in patients with impaired glucose tolerance. More relevant to this project, endothelial dysfunction improved after 4-week treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of NO substrate, L-arginine, protects against fatty acids induced impairment of endothelial function, improves insulin-stimulated microvascular. The protocol design was changed to single arm design.
Tracking Information
- NCT #
- NCT03012386
- Collaborators
- Washington University School of Medicine
- Investigators
- Principal Investigator: Cyndya Shibao, MD Vanderbilt University Medical Center