Insulin-like signaling within and beyond metazoans

Insulin signaling is pivotal in controlling animals' lifespan and responses to environmental changes and, when altered, it may lead to pathogenic states. Despite its importance and relevance for biomedical research, insulin's mechanism of action and the full range of its pathophysiological effects remain incompletely understood. Likewise, the evolutionary origin of insulin and its associated signaling components are unclear. Notwithstanding the common view that insulin signaling originated within metazoans, experimental evidence from non-metazoans suggest a more widespread distribution across eukaryotes. Here, we summarize this evidence. Furthermore, we put forward an evolutionary account that reconciles seemingly contradictory results in the literature.