PANDER Binds to the Liver Cell Membrane and Inhibits Insulin Signaling in HepG2 Cells

FEBS Lett. 2009 Sep 17;583(18):3009-15. doi: 10.1016/j.febslet.2009.08.008. Epub 2009 Aug 14.

Abstract

PANDER is a cytokine co-secreted with insulin from islet beta-cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by (125)I-PANDER saturation and competitive binding assays. In HepG2 cells, pre-treatment with PANDER ranging from 4 pM to 4 nM for 8h resulted in a maximal inhibition of insulin-stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. Moreover, PANDER treatment also reduced insulin-stimulated PI3K and pAkt levels by 55% and 48%, respectively. In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Cytokines / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Insulin / physiology*
  • Liver / cytology*
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Recombinant Proteins
  • Signal Transduction / drug effects*

Substances

  • Cytokines
  • Insulin
  • PANDER protein, mouse
  • Recombinant Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt