Participation of glucose transporters on atrial natriuretic peptide-induced glucose uptake by adult and neonatal cardiomyocytes under oxygenation and hypoxia

Abstract

Natriuretic peptides, beside their endocrine actions, have paracrine functions which include regulating glucose uptake and metabolism. Atrial natriuretic peptide (ANP) actions are mediated by cGMP which is implicated in the metabolic adaptation of glucose metabolism to oxygen deprivation in the heart. Although, it has been reported that ANP increases glucose uptake, cGMP decreases it. The aim of the present paper was to evaluate the role of the glucose transporters 1 and 4 (GLUTS), in glucose uptake produced by ANP in fatty acid-dependent adult cardiomyocytes and glucose-dependent neonatal cardiomyocytes under oxygenation and hypoxia, which reverts adult metabolism to glucose-dependent. We also explored if the calcium–calmodulin complex participates in ANP-induced increase in glucose uptake. Neonatal cells had a higher glucose uptake than adult cells and GLUT 1 participated in basal uptake in both cell types. Hypoxia increased glucose uptake in adult cardiomyocytes but not in neonatal cells and this increase in glucose uptake was mediated by GLUT4. ANP increased glucose uptake in both adult and neonatal myocytes, under oxygenation and hypoxia, and GLUT4 favored this increase. Neonatal cells were less sensitive to ANP. Trifluoperazine, a calcium–calmodulin blocker, inhibited the ANP-induced increase in glucose uptake. This suggests that ANP promotes GLUT 4 calcium-mediated recruitment to the cell membrane. In conclusion, glucose uptake regulation is one of the paracrine metabolic effects of ANP in adult and neonatal cardiomyocytes under oxygenation and hypoxia. This effect of this peptide could explain the beneficial effects found in the internal medicine and surgical fields.