Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells.
The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [(3)H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake. High resistin levels (50-100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter.
Di Simone
Nicoletta
N
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy. nicolettadisimone@rm.unicatt.it
Di Nicuolo
Fiorella
F
Marzioni
Daniela
D
Castellucci
Mario
M
Sanguinetti
Maurizio
M
D'lppolito
Silvia
S
Caruso
Alessandro
A
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D052243:Resistin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D052243:Resistin; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose