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

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.

Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic blood pressure values and hearth rate in polycystic ovary syndrome

“…It has been shown to stimulate glycose-dependent insulin secretion [28]. Low N1 levels have been reported to be responsible for IR and metabolic syndrome [29].…”

Nucleobindin-2 is a positive regulator for insulin-stimulated glucose transporter 4 translocation in fenofibrate treated E11 podocytes [Rapid Communication]

“…Recently Nucleobindin-2 was reported to regulate insulin secretion, peripheral glucose uptake, and hepatic gluconeogenesis and decreased Nucleobindin-2 expression has been suggested to partly account for several metabolic consequences in diabetic animal models [8][9][10][11]. In addition to the regulation of insulin secretion and sensitivity in peripheral tissues, Nucleobindin-2/ Nesfatin-1 proteins have also been shown to regulate hypothalamic function in the control of hepatic gluapproximately 60-70% (Fig.…”

“…Immunoprecipitations were performed by using 2mg of the cell extracts incubated with 4 μg of a Septin7 polyclonal antibody for 2 hours at 4 o C. The samples were then incubated with protein A-Sepharose for 1 hour at 4 o C. Either immunoprcipitaed samples or whole cell lysates samples were resuspended in SDS sample buffer (125mM Tris-HCl, pH 6.8, 20% (v/v) glycerol, 4% (w/v) SDS, 100mM dithiothreitol, 0.1% ing peripheral glucose uptake in vivo [10]. In addition, Nesfatin-1, but not Nucleobindin-2, was reported to increase glucose uptake and GLUT4 translocation in cardiomyocytes [11].…”

“…1B). Having established transient transfection [9][10][11][12][13][14][15][16] and modified differentiation strategy, we estimated GLUT4 translocation of cultured podocytes with or without fenofibrate treatment using a GLUT4 reporter construct. As shown in Fig.…”

Nesfatin-1: functions and physiology of a novel regulatory peptide

“…However, another study in rats could only confirm the effects on glucose uptake for the adipose tissue (Gonzalez et al 2011a) without detecting changes in insulin signal transduction (Gonzalez et al 2011a). Also in the myocardium, nesfatin-1 augments insulin receptor signaling to increase glucose uptake by mobilization of the glucose transporter, supposedly due to local nesfatin-1 production, which is dependent on diet and coronary health (Feijoo-Bandin et al 2013). Interestingly, in normoglycemic fasted db/db or freely fed wild-type mice (Su et al 2010), blood glucose was not affected by intravenous nesfatin-1, suggesting that nesfatin-1 is able to correct a pathological hyperglycemic state, but is not of relevance in the normoglycemic range.…”