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)iodoTyr'0-glucagon to a peptide metabolite lacking the NH2-terminal three residues of the hormone.The peptide is re- leased 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 con- clude that (a) the glucagon fragment arises from the cell-mediated processing of the hormone on a superficial aspect of the hepatocyte, (b) the glucagon fragment identified during experiments in vitro represents the cognate of a peptide formed during the hepatic metabolism of glucagon in vivo, and (c) measurement of the fragment by COOH-terminal radioimmunoassays could lead to an understimulation of hepatic glucagon extraction.cation of labeled peptides, and the final purification of (1251)iodoTyr10glucagon and ('25I)iodoTyr13-glucagon can be found elsewhere (16, 26).Radiolabeled peptide fragments (for use as molecular weight markers Hepatic Glucagon Metabolism 409