Signaling by insulin-like growth factor 1 in brain

Abstract

The homologous insulin and insulin-like growth factor (IGF) receptors are both expressed in the brain, in overlapping but distinct neuroanatomical patterns. In contrast to insulin, IGF1 is also highly expressed within the brain and is essential for normal brain development. IGF1 promotes projection neuron growth, dendritic arborization and synaptogenesis. IGF1 acts in an autocrine and/or paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3K)/Akt, also known as protein kinase B (PKB)/glycogen synthase kinase 3beta (GSK3beta) pathways similar to insulin signaling in peripheral tissues. IGF1 promotes neuronal survival during normal brain development mainly in hippocampal and olfactory systems that depend on postnatal neurogenesis. IGF1's anabolic and neuroprotective roles may be coordinated by inhibition of GSK3beta. The identification of GSK3beta as a major target of brain IGF1 signaling provides a unifying pathway for IGF1's well-established anabolic and anti-apoptotic functions, with IGF1-induced inhibition of GSK3beta triggering multifaceted anabolic and neuroprotective effects.