Insulin receptor (IR)

The insulin receptor (IR) is a transmembrane receptor tyrosine kinase that is activated predominantly by insulin and, to a lesser extent, by insulin-like growth factors IGF-1 and IGF-2[3][6][7]. Upon ligand binding, IR undergoes autophosphorylation and initiates a complex intracellular cascade, principally via the insulin receptor substrate (IRS) proteins and downstream PI3K/Akt and MAPK signaling pathways[1][5][7][8]. IR plays a critical role in glucose uptake (notably through the translocation of GLUT4), anabolic metabolism, regulation of lipid synthesis, cell survival, growth, and gene expression[1][3][5][7]. Dysfunction of insulin receptor signaling is directly implicated in the pathogenesis of diabetes mellitus (especially type 2), metabolic syndrome, various cancers (where IR overactivation and isoform switching are linked to cell proliferation and therapy resistance), as well as neurodegenerative and cardiovascular diseases[2][4][6]. The INSR gene encodes the receptor, which is expressed across most tissues and exists primarily in two isoforms (IR-A and IR-B) due to alternative splicing; these isoforms have distinct roles in development, metabolism, and mitogenesis[3][4][6]. Therapeutic targeting of IR is established in metabolic diseases (using insulin) and is under investigation for cancer therapy where dual inhibition of IR and IGF-1R may be beneficial[4][6]. Research drugs affecting IR function include kinase inhibitors and monoclonal antibodies used predominantly in preclinical and early-phase clinical settings[6]. Note: The queried term "Insulin receptor signaling" describes a **pathway** (a process), not a discrete molecular target, so this entry has been normalized to "Insulin receptor," the canonical and actionable molecular entity[3][6][7].

Other names

Insulin receptor tyrosine kinaseINSRIR-AIR-B

Agonists: Activate IR to promote downstream metabolic signaling, leading to increased glucose uptake, gene regulation, and anabolic responses - Antagonists/inhibitors: Block IR signaling to reduce mitogenic effects, particularly in cancer