Degradation of 125I-Glucagon, -Pancreatic Polypeptide and -Insulin by Acid Saline Extract of Rat Submaxillary Gland and Their Protection by Proteinase Inhibitors.

Abstract

The acid saline extract (ASE) of rat submaxillary gland exerts a powerful degrading effect on 125I-glucagon. In order to study the degradation of other 125I-peptides by ASE and the effects of their inhibitors , 125I-pancreatic polypeptide (PP) and 125I-insulin were used together with 125I-glucagon. The degradation studies were done by the trichloroacetic acid (TCA) method or gel in the ordinary immunoassay system using the TCA method, but 125I-insulin was intact in the presence of ASE. Leupeptin, and to a lesser extent pchloromercuriphenyl-sulfonic acid (PCMS) and N-ethylmaleimide, inhibited the destruction of 125I-glucagon or -PP under the TCA method. PCMS was especially protective at high concentrations, for example 16 mM. These findings were confirmed by gel filtration of the assay mixture. In the presence of leupeptin (0.4mM) and PCMS (16mM), no shift in the peak of labelled glucagon or PP occurred. Thus ASE degrades not only 125I-glucagon but -PP, and thiol proteinase inhibitors have a strong inhibitory action on them.

Oral Delivery of Insulin for Treatment of Diabetes: Classical Challenges and Current Opportunities

“…Enzyme inhibitors slow the rate of degradation of insulin, which increases the amount of insulin available for absorption. This review article revealed the use of different protease inhibitors resulting in significant hypoglycemic effects which include aprotinin (Ziv et al, 1987;Morishita et al, 1993;Laurenti et al, 1996;Kimura et al, 1996;Morimoto et al, 2000;Radwan and Aboul-Enein, 2002;Katayama et al, 2003;Cilek et al, 2005;Park et al, 2007;Jelvehgari et al, 2011;Boateng et al, 2014) bacitracin (Yamamoto et al, 1994;Kimura et al, 1996;Bernkop-Schnurch, 1998;Park et al, 2007;Su et al, 2012;Balabushevich et al, 2013;Jose et al, 2013) camostat mesilate (Yamamoto et al, 1994;Ogiso et al, 1997;Tozaki et al, 2001;Del Curto et al, 2009), leupeptin (Tasaka et al, 1989;Liu et al, 2003) and diethylene triaminepentaacetic acid (Su et al, 2012).…”