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Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans
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.
Details
| Lead sponsor | Vanderbilt University Medical Center |
|---|---|
| Phase | Phase 1/Phase 2 |
| Status | COMPLETED |
| Enrolment | 26 |
| Start date | 2017-01 |
| Completion | 2021-07-31 |
Conditions
- Insulin Resistance
- Endothelial Dysfunction
Interventions
- Sildenafil Citrate in G allele carrier
- Sildenafil Citrate in non G allele carrier
Primary outcomes
- Change in Microvascular Blood Volume (MBV) During Insulin Infusion — Baseline to end of procedure (approximately 180 minutes)
Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity. MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180). - Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups — Baseline to 4 weeks
Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity . Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
Countries
United States