The Effects of Insulin on Immortalized Rat Schwann Cells, IFRS1

Int J Mol Sci. 2021 May 23;22(11):5505. doi: 10.3390/ijms22115505.

Abstract

Schwann cells play an important role in peripheral nerve function, and their dysfunction has been implicated in the pathogenesis of diabetic neuropathy and other demyelinating diseases. The physiological functions of insulin in Schwann cells remain unclear and therefore define the aim of this study. By using immortalized adult Fischer rat Schwann cells (IFRS1), we investigated the mechanism of the stimulating effects of insulin on the cell proliferation and expression of myelin proteins (myelin protein zero (MPZ) and myelin basic protein (MBP). The application of insulin to IFRS1 cells increased the proliferative activity and induced phosphorylation of Akt and ERK, but not P38-MAPK. The proliferative potential of insulin-stimulated IFRS1 was significantly suppressed by the addition of LY294002, a PI3 kinase inhibitor. The insulin-stimulated increase in MPZ expression was significantly suppressed by the addition of PD98059, a MEK inhibitor. Furthermore, insulin-increased MBP expression was significantly suppressed by the addition of LY294002. These findings suggest that both PI3-K/Akt and ERK/MEK pathways are involved in insulin-induced cell growth and upregulation of MPZ and MBP in IFRS1 Schwann cells.

Keywords: Akt; Schwann cells; extracellular-signal-regulated kinase (ERK); insulin; myelin associated glycoprotein; myelin basic protein; myelin protein zero.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line, Transformed
  • Chromones / pharmacology
  • Diabetic Neuropathies / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Insulin / pharmacology*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Morpholines / pharmacology
  • Myelin Proteins / biosynthesis
  • Myelin Proteins / genetics
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphorylation
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptor, Insulin / biosynthesis
  • Receptor, Insulin / genetics
  • Schwann Cells / drug effects*
  • Signal Transduction / drug effects

Substances

  • Chromones
  • Flavonoids
  • Insulin
  • Morpholines
  • Myelin Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Receptor, Insulin
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one