Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 OC19.4

CR-CHUM, University of Montreal, Montreal, QC, Canada.


We have uncovered the entire functional oxytocin (OT) system in the rat and human heart. In the experimentally-induced myocardial infarction (MI) in rats, the continuous OT delivery improves the cardiac work, reduces inflammation, and stimulates angiogenesis. We hypothesized that these actions of OT are mediated by increase in glucose uptake in cardiomyocytes (CM). Indeed OT (10 nM) increased basal glucose uptake in CM to 4.0±0.2 fmol/mg protein in comparison to 2.2 fmol/mg in control cells (P<0.001). OT had a moderate synergistic effect with 0.1 mM 2, 4-dinitrophenol (a hypoxia-inducing agent, DNP), augmenting basal glucose uptake to 5.5±0.5 fmol/mg. Wortmannin (0.1 μM), an inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly suppressed OT and insulin (10 nM) (P<0.001) effects on glucose uptake, indicating a common pathway. The activation of PI3K pathway suggested beneficial effects of OT in prevention of CM hypertrophy. Analysis of the cells treated with OT revealed accumulation of ANP in perinuclear region and its co-localization with mitochondria without changes of cell size. Further study demonstrated that OT inhibits CM hypertrophy induced by GqPCR agonists such as endothelin-1, inhibits CM apoptosis and decreases oxydative stress after exposure to ischemia-reoxygenation, the conditions, mimicking the myocardial infarction. The pre-treatment of cells with OT (10 nM) completely inhibited the hypertrophic effect induced by ET-1 both in the newborn and adult rat CM. The OT receptor antagonist and cGMP inhibition abrogated the anti-hypertrophic effect of OT. Furthermore, Western blot analysis indicated that OT treatment modulates phosphorylation of proteins downstream of PI3K such as PKB/Akt. In summary, these findings suggest that OT cardioprotective action is due at least in part to stimulation of PI3K signaling pathway and ANP accumulation in CM. Therefore, in pathological conditions, OT plays a cardioprotective role, and improves vascular and metabolic functions, thus OT presents potential for therapeutic use.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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