Nesfatin-1 in human and murine cardiomyocytes: synthesis, secretion, and mobilization of GLUT-4.

Autores de IIS La Fe

• Manuel Portoles Sanz

  Autor

• 

  Esther Roselló Lletí

  Autor

• Jose Miguel Rivera Otero

  Autor

• Carlos Gonzalez Juanatey

  Autor

• José Francisco Dolz Lago

  Autor

Participantes ajenos a IIS La Fe

• Feijóo-Bandín S
• Rodríguez-Penas D
• García-Rúa V
• Mosquera-Leal A
• Otero MF
• Pereira E
• Rubio J
• Martínez I
• Seoane LM
• Gualillo O
• Calaza M
• García-Caballero T
• Diéguez C

Grupos

• Grupo de Investigación Clínica y Traslacional en Cardiología

Abstract

Nesfatin-1, a satiety-inducing peptide identified in hypothalamic regions that regulate energy balance, is an integral regulator of energy homeostasis and a putative glucose-dependent insulin coadjuvant. We investigated its production by human cardiomyocytes and its effects on glucose uptake, in the main cardiac glucose transporter GLUT-4 and in intracellular signaling. Quantitative RT-PCR, Western blots, confocal immunofluorescence microscopy, and ELISA of human and murine cardiomyocytes and/or cardiac tissue showed that cardiomyocytes can synthesize and secrete nesfatin-1. Confocal microscopy of cultured cardiomyocytes after GLUT-4 labeling showed that nesfatin-1 mobilizes this glucose transporter to cell peripherals. The rate of 2-deoxy-D-[(3)H]glucose incorporation demonstrated that nesfatin-1 induces glucose uptake by HL-1 cells and cultured cardiomyocytes. Nesfatin-1 induced dose- and time-dependent increases in the phosphorylation of ERK1/2, AKT, and AS160. In murine and human cardiac tissue, nesfatin-1 levels varied with diet and coronary health. In conclusion, human and murine cardiomyocytes can synthesize and secrete nesfatin-1, which is able to induce glucose uptake and the mobilization of the glucose transporter GLUT-4 in these cells. Nesfatin-1 cardiac levels are regulated by diet and coronary health.