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) increase... More
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.
