Insulin receptor isoform A (IR-A)

Insulin receptor isoform A is a transmembrane receptor tyrosine kinase produced by alternative splicing of the *INSR* gene, lacking exon 11 and thus missing a 12-amino acid segment in its extracellular domain[1][10]. While both IR-A and IR-B bind insulin, IR-A has a higher affinity for insulin-like growth factor II (IGF-II) and is preferentially expressed in fetal tissues, certain adult tissues (brain, lymphatic, embryonic), and a wide range of tumors[1][7]. IR-A promotes both metabolic and mitogenic (growth-promoting) responses, in contrast to isoform B, which is mainly involved in classic metabolic insulin signaling in adult tissues[1][4]. This unique profile implicates IR-A in cancer development, diabetes, and other diseases linked to altered growth signaling or metabolism. IR-A is considered a key therapeutic target in metabolic disease and cancer research, with its distribution and function being significant determinants of drug responses and disease states[2][7]. Caveats: Some early studies may not distinguish clearly between IR-A and the general insulin receptor; context is critical when mapping disease roles or drug effects specifically to the A isoform. No currently approved drugs selectively target IR-A, but it is an active area of research due to its role in cancer and metabolic disease biology.

Other names

IR-Ashort form insulin receptorexon 11– isoforminsulin receptor (exon 11–)INSR-A

Ligand (insulin, IGF-II) binding triggers autophosphorylation of β-subunits and activation of downstream PI3K/Akt and Ras/MAPK signaling cascades. Promotes glucose uptake, cell growth, differentiation, and inhibits apoptosis.