Evaluation of the Effect of Insulin towards the Activity of Drug-Metabolizing Enzymes (DMEs)

Insulin, a peptide hormone produced by beta cells in the pancreas, is a hormone playing an important role in the regulation of the level of glucose in the blood. The injection of insulin is an efficient therapeutic method to treat diabetes. The adverse effects of overdosing of insulin were evaluated in this study through investigating the inhibition potential of insulin towards various isoforms of UDP-glucuronosyltransferases (UGTs). Recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed as the probe reaction, and 50 mu g/mL of insulin was added to investigate the inhibition potential; 50 mu g/mL of insulin was selected as the initial screening concentration to determine the inhibition of insulin towards the activity of UGT isoforms. Fifty mu g/mL of insulin did not show significant inhibition towards UGT1A1, UGT1A3, UGT1A8, and UGT2B7. However, 50 ug/mL of insulin has been demonstrated to exert significant inhibition towards UGT1A7 (p < 0.001) and UGT1A9 (p < 0.001). In conclusion, the risk of overdosing of insulin was indicated in this study due to the inhibition of insulin towards the activity of UGT1A7 and UGT1A9.