Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 307, Issue 12, Pages E1097-E1104Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00216.2014
Keywords
epoxyeicosatrienoic acids; contrast ultrasound; insulin; muscle blood flow
Categories
Funding
- National Institutes of Health (NIH) [R01-DK-063508, R01-HL-078610, RC1-HL-100659]
- NIH [KL2-TR-000152]
- American Heart Association [12CRP11890055]
Ask authors/readers for more resources
Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects. Contrast-enhanced ultrasound (CEU) was performed to quantify skeletal muscle capillary blood volume (CBV) and MBF in wild-type and obese insulin-resistant (db/db) mice after administration of vehicle or trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (t-AUCB), an inhibitor of soluble epoxide hydrolase that converts EETs to less active dihydroxyeicosatrienoic acids. Similar studies were performed in rats pretreated with L-NAME. CEU was also performed in rats undergoing a euglycemic hyperinsulinemic clamp, half of which were pretreated with the epoxygenase inhibitor MS-PPOH to inhibit EET synthesis. In both wild-type and db/db mice, intravenous t-AUCB produced an increase in CBV (65-100% increase at 30 min, P < 0.05) and in MBF. In db/db mice, t-AUCB also reduced plasma glucose by similar to 15%. In rats pretreated with L-NAME, t-AUCB after produced a significant approximate to 20% increase in CBV, indicating a component of vascular response independent of nitric oxide (NO) production. Hyperinsulinemic clamp produced a time-dependent increase in MBF (19 +/- 36 and 76 +/- 49% at 90 min, P = 0.026) that was mediated in part by an increase in CBV. Insulin-mediated changes in both CBV and MBF during the clamp were blocked entirely by MS-PPOH. We conclude that EETs are a mediator of insulin-mediated augmentation in skeletal muscle perfusion and are involved in regulating changes in CBV during hyperinsulinemia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available