title: Magnetic labeling of pancreatic β-cells modulates the glucose- and insulin-induced phosphorylation of ERK1/2 and AKT.
abstract: This study was undertaken to investigate the effect of a magnetic resonance imaging (MRI) contrast agent, superparamagnetic iron oxide nanoparticle (SPIO), on signal transduction by glucose and insulin in pancreatic β-cells. INS-1 cells were labeled in culture medium containing clinically approved SPIO for 24 h. Labeled and unlabeled cells were stimulated with glucose (25 mM) or insulin (0.1-1 µM) for 12 h. The phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B (AKT) and intracellular insulin protein levels were assessed by Western blotting. After labeling with increasing amounts of SPIO, cytotoxicity was not observed, yet the intracellular iron concentration increased in a dose-dependent manner. SPIO labeling (200 µg Fe ml(-1)) induced a significant increase in ERK1/2 and AKT phosphorylation (labeled vs unlabeled, p < 0.05), but significantly reduced the glucose-stimulated phosphorylation of ERK1/2 and AKT and insulin-stimulated phosphorylation of AKT (labeled vs unlabeled, p < 0.05). The level of intracellular insulin protein was found to be lower in labeled cells than unlabeled cells (labeled vs unlabeled, p < 0.05). This study demonstrates that SPIO labeling alters some fundamental functional variables, at least in INS-1 cells, through modulation of the glucose- or insulin-induced activation of ERK1/2 and AKT, which leads to insulin biosynthesis.
authors.affiliation: Department of Radiology, Seoul National University Hospital, Daehangno, Jongno-gu, Korea.
authors.forename: Hoe Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Lianji
authors.initials: L
authors.lastname: Tian
authors.forename: Shunmei
authors.initials: S
authors.lastname: Lin
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Cha
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000009:adverse effects* / Q000494:pharmacology; D005290:Ferric Compounds / Q000009:adverse effects* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000009:adverse effects*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D007328:Insulin; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose