IGF-I and IGF-II protect cultured hippocampal and septal neurons against calcium-mediated hypoglycemie damage

Bin Cheng, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Insulin and insulin-like growth factors I and II (IGF-I and IGF-II) have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action in the brain are unknown. Since central neurons are particularly vulnerable to hypoglycemia that results from ischemia or other insults, we tested the hypothesis that growth factors can protect central neurons against hypoglycemie damage in vitro. IGF-I and IGF-II (3-100 ng/ml) each prevented glucose deprivation-induced neuronal damage in a dose-dependent manner in rat hippocampal and septal cell cultures. High concentrations of insulin (greater than 1 μg/ml) also protected neurons against hypoglycemie damage. Epidermal growth factor did not protect against hypoglycemie damage. Both IGFs and insulin were effective when administered 24 hr before or immediately following the onset of glucose deprivation. Direct measurements of intraneuronal calcium levels and manipulations of calcium influx demonstrated that calcium influx and sustained elevations in intraneuronal calcium levels mediated the hypoglycemic damage. IGF-I and IGF-II each prevented the hypoglycemia-induced elevations of intraneuronal free calcium. Studies with excitatory amino acid receptor antagonists and calcium channel blockers indicated that NMDA receptors did, and L-type calcium channels did not, play a major role in hypoglycemie damage. Taken together, these findings indicate that IGFs can stabilize neuronal calcium homeostasis and thereby protect against hypoglycemic damage.

Original languageEnglish (US)
Pages (from-to)1558-1566
Number of pages9
JournalJournal of Neuroscience
Volume12
Issue number4
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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