New insights into the signaling system and function of insulin in fish

Fish have provided essential information about the structure, biosynthesis, evolution, and function of insulin (INS) as well as about the structure, evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it is not clear if they arose from a common gene duplication event or from multiple separate gene duplications. INS is produced by the endocrine pancreas of fish as well as by several other tissues, including brain, pituitary, gastrointestinal tract, and adipose tissue. INS regulates various aspects of feeding, growth, development, and intermediary metabolism in fish. The actions of INS are mediated through the insulin receptor (IR), a member of the receptor tyrosine kinase family. IRs are widely distributed in peripheral tissues of fish, and multiple IR subtypes that derive from distinct mRNAs have been described. The IRs of fish link to several cellular effector systems, including the ERK and IRS–PI3k–Akt pathways. The diverse effects of INS can be modulated by altering the production and release of INS as well as by adjusting the production/surface expression of IR. The diverse actions of INS in fish as well as the diverse nature of the neural, hormonal, and environmental factors known to affect the INS signaling system reflects the various life history patterns that have evolved to enable fish to occupy a wide range of aquatic habitats.

► Fish serve as models for pancreatic function and development.
► Insulin is produced by the pancreas and extrapancreatic tissues in fish.
► Regulation of insulin release and action are species- and tissue-specific.
► Fish insulin and insulin receptor have been conserved throughout evolution.
► Insulin signaling in fish includes MAPK/ERK, Akt/PKB, and TOR.