Insulin degradation is a finely tuned process that plays a major role in controlling insulin action and most evidence supports IDE (insulin-degrading enzyme) as the primary degradative agent. However, the biomolecular mechanisms involved in the interaction between IDE and its substrates are often obscure, rendering quite difficult to target the specific enzyme activity. On the other hand, biometals, such as copper, aluminum and zinc, have an important role in pathological conditions such as Alzheimer’s disease or diabetes mellitus. The metabolic disorders connected with the latter lead to some metallostasis alterations in the human body and many studies point at a high level of interdependence between diabetes and several cations. We have previously reported (Grasso et al., Chem.- Eur. J. 17 (2011) 2752–2762) that IDE activity towards Aβ peptides can be modulated by metal ions. Here, we have investigated the effects of different metal ions on the IDE proteolytic activity towards insulin as well as a designed peptide comprising a portion of the insulin B chain (B20-30), which has a very low affinity for metal ions. The results obtained by different experimental techniques clearly show that IDE is irreversibly inhibited by copper(I) but is still able to process its substrates when it is bound to copper(II).
|Titolo:||Metal ions affect insulin-degrading enzyme activity|
|Data di pubblicazione:||2012|
|Appare nelle tipologie:||1.1 Articolo in rivista|