Studies on insulin degradation inside the pancreatic B-cell: evidence for a regulating role of glucose

The present study aimed at testing whether insulin degradation inside the pancreatic B-cell is regulated by insulin release or by glucose per se. Radioactively prelabelled isolated rat islets were cultured in unlabelled medium for 24 h. During that chase period the media contained (a) 50 or 300 mg glucose/dl alone or (b) together with 100 micrograms diazoxide/ml and (c) 50 mg glucose/dl without or with 10 mM L-leucine or 300 mg glucose/dl. The content of labelled (pro-)insulin in islets and media was measured and related to degradation. No degradation was found at the high glucose concentration, not even when insulin release was blocked by diazoxide. Degradation was also inhibited in the presence of leucine. The results suggest that glucose per se or its metabolism prevents insulin from being degraded inside the B-cell.