Quantitative aspects of secretion and hepatic removal of glucagon in sheep.

The secretion of immunoreactive glucagon (IRG) into the portal blood and its removal by the liver were determined in conscious-fed sheep by simultaneous measurement of venoarterial plasma concentration differences and portal and hepatic plasma flows. IRG was determined using Manns' antiserum and Unger's 30K antiserum, the latter being highly specific for pancreatic glucagon. In 21 experiments in which Manns' antiserum was used the IRG secretory rate was 7.1 +/- u.4 mug/h. The value using 30K antiserum was lower (5.5 +/- 1.3, n=6), but not significantly different. Although the hepatic extraction ratio (hepatic removal - total IRG presented to the liver) was only 7%, the hepatic removal of 2.4 +/- 0.5 mug/h was equivalent to 31-35% of the portal IRG secretory rate. Since during steady-state conditions, glucagon secretion equals glucagon removal, the liver must account for approximately one-third of the glucagon degraded by the entire body.