Insulinbinding

Insulinbinding, also written as insulin binding, refers to the interaction of insulin with cell-surface receptors that mediate its biological effects. The primary receptor is the insulin receptor (IR), a transmembrane tyrosine kinase expressed in most mammalian tissues. Insulin binding occurs at the extracellular α-subunits of the IR, prompting conformational changes that activate intrinsic tyrosine kinase activity in the β-subunits and trigger phosphorylation cascades inside the cell.

IR exists as two isoforms generated by alternative splicing of the INSR gene: IR-A and IR-B. IR-A is more prevalent in fetal tissue and some cancers and has a higher affinity for IGF-2, whereas IR-B is more related to metabolic signaling. Insulin binding promotes phosphorylation of insulin receptor substrates (IRS proteins), activation of PI3K and AKT pathways, and/or the MAPK pathway, leading to diverse responses including translocation of the glucose transporter GLUT4 to the plasma membrane, increased glucose uptake, glycogen synthesis, lipid synthesis, and protein synthesis.

Binding dynamics depend on receptor density, insulin concentration, and receptor endocytosis. Binding is reversible and subject to desensitization with prolonged exposure. In addition to the canonical IR, insulin can weakly interact with IGF-1 receptors under high hormone concentrations, contributing to mitogenic signaling.

Clinical relevance includes insulin resistance and type 2 diabetes, where receptor signaling is impaired; mutations in INSR can cause severe insulin resistance syndromes; autoantibodies or antibodies against insulin can alter binding. Analysis of insulin binding uses radiolabeled insulin binding assays, competition binding, and newer biophysical methods such as surface plasmon resonance.