Insulin receptor isoform B (IR-B) (IR-B)

The Insulin receptor isoform B (IR-B) is a transmembrane receptor tyrosine kinase that plays a central role in regulating systemic glucose homeostasis and metabolism (UniProt P06213). It is a splice variant of the INSR gene that includes the 12 amino acids encoded by exon 11, distinguishing it from the shorter isoform A (Belfiore et al., 2009, Endocrine Reviews). IR-B is predominantly expressed in adult metabolic tissues such as the liver, skeletal muscle, and adipose tissue, where it exhibits high affinity for insulin and mediates its metabolic effects (Belfiore et al., 2017, Frontiers in Endocrinology). Upon insulin binding, the receptor undergoes autophosphorylation, triggering downstream signaling pathways like the PI3K/Akt cascade, which facilitates glucose uptake via GLUT4 translocation (PubMed: 28837468). Dysregulation or decreased sensitivity of IR-B is a hallmark of type 2 diabetes and insulin resistance syndromes (NIH, Gene ID: 3643). Pharmacological targeting of this receptor primarily involves insulin analogs designed to mimic endogenous insulin action for the management of hyperglycemia (StatPearls: Insulin). In addition to metabolic regulation, IR-B signaling also influences protein synthesis and cell growth in target tissues (UniProt P06213). The balance between IR-A and IR-B isoforms is critical, as shifts in splicing are observed in various disease states, including cancer and metabolic disorders (Belfiore et al., 2009).

Other names

INSR isoform BInsulin receptor long isoformInsulin receptor splice variant BIR-B

Binding of insulin to the extracellular alpha subunits of the receptor induces a conformational change that activates the intrinsic tyrosine kinase activity of the intracellular beta subunits (UniProt P06213). This leads to autophosphorylation and the recruitment of insulin receptor substrates (IRS), which activate the PI3K/Akt and MAPK pathways to regulate glucose uptake and metabolism (PubMed: 28837468).