ABSTRACT
The retina is one of the numerous insulin-sensitive tissues. Studies conducted in mice, rats, and rabbits have shown that the insulin receptor (IR) has a high basal kinase activity in retina that does not fluctuate with feeding or fasting. By contrast, IR activity in the liver varies markedly with fasting (low plasma insulin levels,
low IR activity) and feeding (high plasma insulin levels, high IR activity). The IR, along with insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor-related receptor (IRR), belongs to a family of heterotetrameric (α2β2) transmembrane glycoprotein receptors that are widely expressed in mammalian tissues. Although little is known about the IRR, the IR and IGF-1R are the products of different genes that lead to the expression of proreceptors that display more than 50% amino acid sequence identity. The IR family ligands include three structurally related peptides that also present a high amino acid sequence identity: insulin, IGF-1, and IGF-2. Posttranslational processing results in the dimerization and disulfide linkage of proreceptors followed by proteolytic cleavage that generates α and β subunits (1). The extracellular α subunit contains the ligand-specific binding site, and the transmembrane β subunit possesses the tyrosine kinase activity. The kinase activity is induced by the interaction of the ligand with the α subunit that induces the transautophosphorylation of the β subunits.
