Biochemical and cellular properties of insulin receptor signalling

Formally started in 1971 with the discovery of the insulin receptor, the field of insulin signalling has by now resolved many questions related to the cellular, biochemical foundation of the hormone's biological effects.The three major biochemical steps in insulin signalling are: tyrosine phosphorylation of the receptor and its direct substrates; activation of the lipid kinase, PI3K; and activation of multiple serine/threonine kinases, the most important of which is AKT.Through various combinations of these signalling modules in different cell types, with different time and dose dependence after insulin binding, innumerable combinations of signalling complexes can be obtained. This diversity likely underpins the pleiotropism of insulin action, as well as the pathogenesis of insulin resistance.Key recent discoveries in the field include the delineation of a pathway to insulin-dependent glucose transport, the emergence of two central pathways for regulation of gene expression, the interaction of insulin and leptin signalling in the CNS to facilitate energy homeostasis, and the role of inflammation as a regulator of insulin signalling.