Abstract 15114: Effects of Apelin on Forearm Vasodilator Function During Hyperinsulinemia in Patients With Central Obesity
Patients with central obesity (CO) have impaired insulin-stimulated vasodilation, which may be involved in the development of hypertension and contribute to insulin resistance by affecting the glucose uptake. Apelin, a peptide hormone acting as an adipokine, stimulates insulin sensitivity and induces nitric oxide (NO)-dependent vasodilation in healthy subjects. We examined the effects of exogenous apelin on resting blood flow and on insulin-stimulated, NO-dependent vasodilation in patients with CO by use of the forearm perfusion technique. Forearm blood flow (FBF) responses to intra-arterial infusion of graded doses of acetylcholine (ACh; stimulus for endothelial release of NO) and sodium nitroprusside (SNP; exogenous NO donor) were assessed in 20 patients with CO during coinfusion of either saline (n=11) or regular insulin (0.15 mU/Kg/min; n=9). Thereafter, patients underwent to intra-arterial infusion of apelin (1.5 nmol/min for 30 minutes) and responses to ACh and SNP were then reassessed in both groups. Apelin administration resulted in a significant increase in unstimulated FBF both in the absence (from 3.7±0.3 [mean±SEM] to 5.3±0.4 ml/min/dl; P=0.005) and in the presence of hyperinsulinemia (from 4.1±0.5 to 5.8±0.8 ml/min/dl; P=0.001), without difference between the 2 conditions (P=0.80). In the absence of hyperinsulinemia, however, apelin did not affect vascular responses to either ACh (P=0.26) or SNP (P=0.12). In the presence of hyperinsulinemia, by contrast, apelin infusion was associated with a significant improvement in vascular reactivity to both ACh (P=0.03) and SNP (P=0.02). In conclusion, the physiological vasodilator properties of apelin are preserved in blood vessels of patients with CO and exogenous apelin is able to improve both endothelium-dependent and -independent insulin-stimulated vasodilator responsiveness in these patients. These findings suggest that apelin, in addition to direct vasodilator actions, exerts beneficial effects to correct insulin signaling abnormalites in vascular smooth muscle cells of patients with CO. As a consequence, strategies targeting the apelin/APJ system might favorably affect both hemodynamic abnormalities and impaired glucose disposal in insulin resistance states like CO.
- © 2013 by American Heart Association, Inc.