Insulin receptor isoform B (IR-B)

The Insulin receptor isoform B (IR-B) is a transmembrane receptor tyrosine kinase and one of two major isoforms of the insulin receptor (INSR) produced by alternative splicing of exon 11. Unlike the IR-A isoform, IR-B includes a 12-amino acid sequence encoded by exon 11, which confers a higher specificity for insulin over insulin-like growth factors (IGFs). IR-B is predominantly expressed in adult, well-differentiated metabolic tissues such as the liver, skeletal muscle, and adipose tissue, where it serves as the primary mediator of insulin's metabolic actions, including glucose uptake, glycogen synthesis, and lipid metabolism. In pancreatic beta cells, IR-B specifically promotes the transcription of the glucokinase gene, acting as a glucose sensor. Dysfunction or reduced expression of IR-B is a hallmark of insulin resistance and type 2 diabetes, often characterized by a shift in the IR-A/IR-B ratio toward the more mitogenic IR-A isoform. While IR-B is primarily associated with metabolic signaling, its counterpart IR-A is more linked to mitogenic and fetal growth processes. Therapeutic strategies targeting IR-B include various insulin analogs and emerging small-molecule activators designed to restore metabolic homeostasis. However, pharmacological activation of the insulin receptor carries risks such as hypoglycemia and potential mitogenic effects if the signaling is not sufficiently biased toward the metabolic pathway.

Other names

INSR isoform BInsulin receptor BIR-BInsulin receptor long isoformExon 11+ insulin receptorCD220

Agonism of the receptor tyrosine kinase, leading to autophosphorylation of the beta-subunit and activation of the PI3K/Akt and MAPK signaling pathways.