Role of GALNT2 in the modulation of ENPP1 expression, and insulin signaling and action. GALNT2: A novel modulator of insulin signaling

Antonella Marucci, Flora Cozzolino, Claudia Dimatteo, Maria Monti, Piero Pucci, Vincenzo Trischitta, Rosa Di Paola

Research output: Contribution to journalArticlepeer-review

Abstract

Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling and action. Understanding the mechanisms underlying ENPP1 expression may help unravel molecular mechanisms of insulin resistance. Recent data suggest a role of ENPP1-3'untraslated region (UTR), in controlling ENPP1 expression. We sought to identify trans-acting ENPP1-3'UTR binding proteins, and investigate their role on insulin signaling.By RNA pull-down, 49 proteins bound to ENPP1-3'UTR RNA were identified by mass spectrometry (MS). Among these, in silico analysis of genome wide association studies and expression profile datasets pointed to N-acetylgalactosaminyltransferase 2 gene (GALNT2) for subsequent investigations. Gene expression levels were evaluated by RT-PCR. Protein expression levels, IRS-1 and Akt phosphorylation were evaluated by Western blot. Insulin receptor (IR) autophosphorylation was evaluated by ELISA.GALNT2 down-regulation increased while GALNT2 over-expression reduced ENPP1 expression levels. In addition, GALNT2 down-regulation reduced insulin stimulation of IR, IRS-1 and Akt phosphorylation and insulin inhibition of phosphoenolpyruvate carboxykinase (PEPCK) expression, a key neoglucogenetic enzyme.Our data point to GALNT2 as a novel factor involved in the modulation of ENPP1 expression as well as insulin signaling and action in human liver HepG2 cells.

Original languageEnglish
Pages (from-to)1388-1395
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • 3'UTR binding proteins
  • ENPP1
  • GALNT2
  • Insulin signaling

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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