The many faces of insulin-like peptide signalling in the brain

Key Points Insulin-like peptides (ILPs), which comprise insulin, insulin-like growth factor 1 (IGF1) and IGF2, influence overall brain development by affecting proliferation, survival and differentiation of brain cells and by having modulatory roles in the refinement of brain circuitries. Peripheral ILPs enter the brain through the blood–cerebrospinal fluid barrier and blood–brain barrier in a tonic fashion (dependent on circulating levels) and in a phasic manner according to local brain activity. The adult brain is a major target of ILPs; here, they act as modulators of synaptic plasticity to orchestrate and control energy allocation. We propose that central and peripheral ILPs cooperate as a functional network in brain physiology and disease. The brain is a major target of insulin and insulin-like growth factors (IGFs). Fernandez and Torres-Alemán describe how these peptides enter the CNS to reach specific brain areas and review their actions in the developing and adult brain. They propose that insulin and IGFs regulate diverse processes that are all ultimately involved in energy homeostasis. Central and peripheral insulin-like peptides (ILPs), which include insulin, insulin-like growth factor 1 (IGF1) and IGF2, exert many effects in the brain. Through their actions on brain growth and differentiation, ILPs contribute to building circuitries that subserve metabolic and behavioural adaptation to internal and external cues of energy availability. In the adult brain each ILP has distinct effects, but together their actions ultimately regulate energy homeostasis — they affect nutrient sensing and regulate neuronal plasticity to modulate adaptive behaviours involved in food seeking, including high-level cognitive operations such as spatial memory. In essence, the multifaceted activity of ILPs in the brain may be viewed as a system organization involved in the control of energy allocation.