Abstract 12120: Endothelial Hyperpolarizing Factors Are Important in Insulin-Mediated Augmentation in Skeletal Muscle Perfusion: A Study Using Contrast Ultrasound Perfusion Imaging
Background: Post-prandial hyperinsulinemia produces an increase in skeletal muscle capillary blood volume (CBV) which is thought to be critical for enhancing glucose uptake. This capillary recruitment is partially mediated by NO. Other endothelial-derived vasodilators have not been evaluated. We hypothesized that insulin-mediated changes in muscle microvascular blood flow (MBF) and CBV are also mediated by epoxyeicosatrienoic acids (EETs)which are endothelial-derived hyperpolarizing factors derived from arachidonic acid metabolism by epoxygenases.
Methods: Eleven Sprague-Dawley rats underwent euglycemic hyperinsulinemic clamp with an insulin infusion rate of 10 mU·min-1·kg-1 I.V. Five rats were treated with the epoxygenase inhibitor N-Methylsulfonyl-6 (2-propargyloxyphenyl) hezanamide (MS-PPOH) given by intraperitoneal osmotic minipump beginning 24 hrs prior to study (0.21mg/hr). Contrast enhanced ultrasound of the proximal hindlimb adductor muscle was performed during a continuous infusion of microbubbles at baseline and at 30 and 90 min after initiation of hyperinsulinemia. MBF and CBV were derived from time-intensity data obtained after a high-power destructive pulse sequence.
Results: At baseline, there was a non-significant reduction in MBF in the MS-PPOH-treated compared to control rats (8.1±4.2 vs. 6.5±2.9 ml/min/100g). During the clamp, there was a time-dependent increase in MBF in control rats (19±36 and 76±49 % at 30 and 90 min, p=0.026), whereas MBF did not increase in the MS-PPOH-treated rats (8±43 and -4±38 % at 30 and 90 min, p=0.758). The increase in MBF in control rats was partially mediated by an increase in CBV (15±16 % at 90 min) whereas CBV tended to decrease with time in the MS-PPOH rats (-18±44 % at 90 min). There were no significant differences in the rate of glucose disposal between the two groups, measured by the glucose infusion rate to maintain euglycemia.
Conclusion: We conclude that the EET family of endothelial hyperpolarizing factors contributes to insulin-mediated augmentation in skeletal muscle perfusion. These data may partially explain beneficial effects on glucose homeostasis that have been found in clinical trials evaluating new therapies that increase EETs.
- © 2013 by American Heart Association, Inc.