Hepatic glucagon metabolism. Correlation of hormone processing by isolated canine hepatocytes with glucagon metabolism in man and in the dog.
We have found that canine and rat hepatocytes convert (125I)iodoTyr10-glucagon to a peptide metabolite lacking the NH2-terminal three residues of the hormone. The peptide is released into the cell incubation medium and its formation is unaffected by a variety of lysosomotropic or other agents. Use of specific radioimmunoassays and gel filtration demonstrated in both normal subjects and in chronic renal failure patients a plasma peptide having the properties of the hormone fragment identified by cell studies. Studies of the dog revealed a positive gradient of the fragment across the liver and no differential gradient of the fragment and glucagon across the kidney. We conclude that the glucagon fragment arises from the cell-mediated processing of the hormone on a superficial aspect of the hepatocyte, the glucagon fragment identified during experiments in vitro represents the cognate of a peptide formed during the hepatic metabolism of glucagon in vivo, and measurement of the fragment by COOH-terminal radioimmunoassays could lead to an understimulation of hepatic glucagon extraction.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D005934:Glucagon / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology
D013004:Somatostatin; D005934:Glucagon