Journal of Neural Transmission

, Volume 112, Issue 2, pp 179–191

Insulin inhibits AMPA-induced neuronal damage via stimulation of protein kinase B (Akt)

  • S.-J. Kim
  • Y. Han

DOI: 10.1007/s00702-004-0163-6

Cite this article as:
Kim, SJ. & Han, Y. J Neural Transm (2005) 112: 179. doi:10.1007/s00702-004-0163-6


We designed a series of experiments to explore the neuroprotective effects of insulin. Insulin significantly inhibited the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced neuronal cell damage as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay. However, insulin had little affect on the AMPA-induced glial cell damage. To determine whether insulin inhibits AMPA-induced excitotoxicity, we performed grease-gap recording assays using rat brain slices. In these experiments, insulin also significantly inhibited AMPA-induced depolarization. Flow cytometry and DNA fragmentation assays showed that insulin inhibits AMPA-induced apoptosis and DNA fragmentation, respectively. Insulin stimulated protein kinase B (Akt) activity, whereas AMPA pretreatment did not alter the insulin-stimulated Akt activity. On the contrary, insulin blocked induction of SAPK/JNK, which AMPA stimulated. Taken together, these results suggest that insulin exerts neuroprotective effects by inhibiting AMPA-induced excitotoxicity and apoptosis, possibly by activating Akt and blocking SAPK/JNK.

Keywords: Insulin, neuroprotection, Akt, JNK.

Copyright information

© Springer-Verlag/Wien 2004

Authors and Affiliations

  • S.-J. Kim
    • 1
  • Y. Han
    • 1
  1. 1.Department of Pharmacology, School of DentistryKyung Hee UniversitySeoulKorea