The insulin receptor is a transmembrane receptor through which the physiological effects of the insulin hormone are achieved. The receptor consists of four polypeptide chains, which come together to form a cylindrical structure. Binding of insulin to this receptor, activates it and induces certain conformational changes, which cause first auto-phosphorylation of the receptor itself, followed by phosphorylation of substrate molecules, including the Insulin Receptor Substrate 1 (IRS1). Phosphorylation of IRS1 and other substrate molecules leads to a cascade of signal transduction and gene activation events, ultimately resulting in the activation of the glucose transporter, Glut4, and its movement from cellular vesicles towards the cell membrane. Glut4 subsequently, mediates the transport of glucose into the cells. Under normal circumstances, once activated by insulin, the insulin-receptor complex is internalized by the cell, and the receptor is thus removed from the membrane. Later, the receptor is recycled back to the membrane, after the insulin part of the complex is destroyed. The uptake of glucose by the cells can be down-regulated by preventing these receptor molecules to return back to the membrane. This situation is seen in cases where there is persistent excess insulin or high blood glucose.
Since the major effect of binding of insulin to its receptor is the uptake of glucose by the cells, defects in the gene encoding for this protein cause 'insulin insensitivity', resulting in disease conditions such as non insulin dependent diabetes mellitus, Rabson-Mendenhall syndrome, leprechaunism, hyperinsulenimic hypoglycemia, or insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN). The INSR gene is expressed maximally in cells that are most responsive to insulin for glucose, lipid and protein metabolism, especially adipose, skeletal muscle and liver.