Disruption of Disulfide Bonds of Insulin Receptor as a Cause of Insulin Resistance

Many theories have been put forward to explain insulin resistance in DM2. The cause of insulin resistance still remained an enigma till date. Defect in insulin signaling pathway is one such possibility considered for insulin resistance in DM2. For insulin signal transduction to occur downstream, the insulin receptor should be in tetrameric, holo-enzyme form so that the conformational changes and auto-phosphorylation steps take place. A prerequisite to this is, linkage of the two α-sub-units and α,β -sub-units of the pair of the dimers by disulfide bonds. Without this, the receptor is in the α,β dimer half-enzyme form, devoid of any binding affinity to the ligand or auto- phosphorylating activity. The article intends to explore, disruption of the disulfide bond formation, as a possible cause of insulin resistance in DM2.