Former Faculty member, Department of internal Medicine, G.I.T.A.M Dental College, Rishikonda, Visakhapatnam, Andhra Pradesh India.
Review Article
World Journal of Advanced Research and Reviews, 2024, 23(02), 328-331
Received on 22 June 2024; revised on 28 July 2024; accepted on 31 July 2024
Palmitoylation is attachment of a palmitoyl group to the cysteine residues of a protein. The intermediary in this process is Palmitoyl CoA, which is formed during the activation of fatty acids in the beta oxidationn of the palmitic acid, consequent to the shift of the energy metabolism to beta oxidation from glycolysis, in DM2.The insulin receptor has cysteine rich domains in the cytosolic portion of the beta sub unit connected by disulfide bonds. It is hypothesized that the palmitoylation forms a thio-ester bond with cystein residues of the beta sub units of the insulin receptor. Depalmitoylation results in substitution of thiol (-SH) in place of the disulfide (S-S) bonds (S-S), due to the hydrolysis by the thio-esterase enzyme. The disulfide bonds are responsible for formation of the functional tettameric form of the insulin receptor. Consequent to the substitution of the SH group in place of S-S group, during depalmitoylation, the functional specificity of the insulin receptor is lost. This leads to the failure of conformational changes and auto- phoshorylation of the beta sub units when insulin binds to the extra cellular insulin binding receptor domain. Also failure of the cascade of phosphorylation of other signalling proteins occurs. Consequently, the failure of the intra- cellular transduction of the signals results in failure of the translocation of the GLUT 4 transporter to the cell membrane. This results in the hyperglycaemia in spite of hyper insulinemia and mo glucose enters into the cell- a state called insulin resistance in DM 2.
Palmitoylation; Insulin receptor; Insulin resistance; Beta oxidation of fats Acetyl CoA; GLUT 4.
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ASV PRASAD. The role of palmitoylation of the insulin receptor in insulin resistance: A hypothesis. World Journal of Advanced Research and Reviews, 2024, 23(2), 328-331. Article DOI: https://doi.org/10.30574/wjarr.2024.23.2.2324