Nesfatin-1 in Human and Murine Cardiomyocytes: Synthesis, Secretion, and Mobilization of GLUT-4

• DOI: 10.1210/en.2013-1497
• Publication Date: 2013-09-25T09:39:51Z
• Authors: Sandra Feijóo-Bandín; Diego Rodríguez-P...; Vanessa García-Rúa; Ana Mosquera-Leal; Manuel Francisco ...; Eva Pereira; José Rubio; Isabel Martínez; Luisa María Seoane; Oreste Gualillo; Manuel Calaza; Tomás García-Caba...; Manuel Portolés; Esther Roselló-Lletí; Carlos Diéguez; Miguel Rivera; José Ramón Gonzál...; Francisca Lago
• Keywords: Male; 0301 basic medicine; Glucose Transporter Type 4; Calcium-Binding Proteins; Nerve Tissue Proteins; Animal Feed; Dietary Fats; Diet; Rats; DNA-Binding Proteins; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Dietary Fats/pharmacology; Glucose; Gene Expression Regulation; Animals; Humans; Nucleobindins; Female; Myocytes, Cardiac; RNA, Messenger; Cells, Cultured

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-[3H]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.