Demonstration of insulin degradation by thiol-protein disulfide oxidoreductase (glutathione-insulin transhydrogenase) and proteinases of pancreatic islets.
Homogenate preparations of pancreatic islets have been found to degrade insulin by cleavage of the interchain disulfide bonds, followed by proteolysis of the resulting A and B chains. A proteolytic system of the pancreatic islets splitting not only 125I-labeled insulin A chain but also 125I-labeled glucagon at pH 7.0, was shown to be activated by glutathione and inhibited by EDTA. The results suggest that pancreatic islets contain both the thiol-protein disulfide oxidoreductase (glutathione : protein-disulfide oxidoreductase, EC 1.8.4.2) and the A and B chain-degrading enzyme(s). The effects of EDTA argue against the implication of cathepsins in insulin breakdown under the experimental conditions employed.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D005934:Glucagon / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology*; D007700:Kinetics; D003012:Microbial Collagenase; D010088:Oxidoreductases / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D005934:Glucagon; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D000681:Amylases; D010447:Peptide Hydrolases; D003012:Microbial Collagenase