We have recently shown that an entire
oxytocin (OT) system, a
peptide and its cognate receptors, is synthesized in the heart. In fetal and newborn hearts, OT exists in its extended three-
amino acid form, OT-
Gly-Lys-Arg (
OT-GKR). OT translocates
glucose transporter type 4 to the plasma membrane in human endothelial cells. Therefore, we hypothesized that the cardiac OT/
OT-GKR system may be involved in the regulation of myocardial
glucose uptake in physiological conditions and during metabolic stress such as
hypoxia. Primary cultures of neonatal rat cardiomyocytes (CM) and cardiac progenitor cells expressing
ATP-binding cassette efflux transporter G2 transporter (stem cell marker) were studied. OT (10 nm) increased basal
glucose uptake in CM to 4.0 +/- 0.2 fmol/mg
protein, with
OT-GKR (10 nm) elevating it to 5.3 +/- 0.4 fmol/mg
protein (P < 0.001) in comparison with 2.2 fmol/mg in control cells. OT had a moderate synergistic effect with 0.1 mm
2,4-dinitrophenol, augmenting basal
glucose uptake to 5.5 +/- 0.5 fmol/mg.
OT-GKR (10 nm) was even more potent in combination with
2,4-dinitrophenol, increasing
glucose uptake to 9.0 +/- 1.0 fmol/mg.
Wortmannin (0.1 microm), an inhibitor of phosphatidylinositol-3-kinase, significantly suppressed the effect of OT and
insulin (10 nm) (P < 0.001), indicating common pathways. Our data suggest that OT and
OT-GKR influence
glucose uptake in neonatal rat CM and may thus play a role in the maintenance of cardiac function and cell survival during metabolic stress.