ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies
作者： Rosa Di Paola , Nunzia Caporarello , Antonella Marucci , Claudia Dimatteo , Claudia Iadicicco
DOI: 10.1371/JOURNAL.PONE.0019462
关键词: Insulin resistance 、 Insulin 、 Internal medicine 、 Carbohydrate metabolism 、 Skeletal muscle 、 Basal (medicine) 、 Insulin oscillation 、 Glucose uptake 、 Insulin receptor 、 Biology 、 Endocrinology 、 General Biochemistry, Genetics and Molecular Biology 、 General Agricultural and Biological Sciences 、 General Medicine
摘要: The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator insulin receptor (IR) activation, plays role on signaling, secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) transfected in HepG2 liver-, L6 skeletal muscle- INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 GSK3-beta Ser9 phosphorylation L6), PEPCK mRNA levels (HepG2) 2-deoxy-D-glucose uptake (L6) studied. GLUT 4 (L6), caspase-3 activation (INS1E) were also investigated. decreased HepG2-K, L6-K, INS1E-K (20%, 52% 11% reduction vs. untransfected cells) twice as much HepG2-Q, L6-Q, INS1E-Q (44%, 92% 30%). Similar data obtained with L6. progressively lower untransfected, HepG2-K HepG2-Q cells (65%, 54%, 23%). (60% increase over basal), totally abolished L6-K L6-Q cells. slightly reduced (13% 25% cells). Glucose-induced 60% almost INS1E-Q. Serum deficiency activated by two, three four folds INS1E, Glyburide-induced 50% isolated human islets from homozygous QQ donors compared those KK KQ individuals. Our clearly indicate that especially when variant is operating, affects signaling metabolism liver-cells both function survival secreting beta-cells, thus representing strong pathogenic factor predisposing resistance, defective abnormalities.
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