Nesfatin-1 in human and murine cardiomyocytes: synthesis, secretion, and mobilization of GLUT-4.
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.
Laboratorio 7, Instituto de Investigaciones Sanitarias de Santiago de Compostela, Hospital Clínico Universitario, Travesía Choupana s/n, 15706 Santiago de Compostela, Spain. francisca.lago.paz@sergas.es.
Sandra
S
Feijóo-Bandín
Diego
D
Rodríguez-Penas
Vanessa
V
García-Rúa
Ana
A
Mosquera-Leal
Manuel Francisco
MF
Otero
Eva
E
Pereira
José
J
Rubio
Isabel
I
Martínez
Luisa María
LM
Seoane
Oreste
O
Gualillo
Manuel
M
Calaza
Tomás
T
García-Caballero
Manuel
M
Portolés
Esther
E
Roselló-Lletí
Carlos
C
Diéguez
Miguel
M
Rivera
José Ramón
JR
González-Juanatey
Francisca
F
Lago
D000821:Animal Feed / Q000032:analysis; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D012333:RNA, Messenger; D005947:Glucose