This N-terminal tripeptide of IGF-I facilitated the in vitro release of acetylcholine with a several hundredfold higher potency (10⁻¹⁰ - 10⁻⁶ M) than intact IGF-I (4 · 10⁻⁸ M), whereas truncated IGF-I lacking the tripeptide GPE, did not show any significant effect. This raises the possibility that GPE may be the active site of IGF-I. - Although the precise mode of action of GPE is still unknown, another study suggests that local administration of GPE is neuroprotective after brain HI injury via glial cells. In addition, systemic administration of GPE showed a more widespread neuroprotective effect. Therefore, GPE may represent a complementary pathway for central and systemic IGF-1's antiapoptotic effects.