Increased “Glucagon Immunoreactivity” in Plasma of Totally Depancreatized Dogs

Abstract

Elevated plasma glucagon immunoreactivity (IRG) observed in overt diabetes and during prolonged fasting is assumed to be the result of increased secretion of pancreatic glucagon. In seven healthy mongrel dogs diabetes was induced by total pancreateetomy During the first two weeks following surgery, porcine NPH (6 to 12 U, once daily) and Regular insulin (6 to 12 U twice daily) were administered. Thereafter, insulin treatment was discontinued and the dogs were fasted for periods up to seven days. Plasma IRG was measured using antiglucagon serum G9-I which is 95 per cent specific for pancreatic glucagon. Fifteen hours after the last insulin injection an intraportal infusion of Regular insulin was given in amounts sufficient to achieve normoglycemia: mean IRG (pg./ml.) was 118 ± 34, a value similar to that observed in the fasting intact animals (134 ± 33). After insulin withdrawal, as fasting continued, plasma IRG increased progressively in all dogs. On Days 5 and 6-7, after insulin withdrawal, when peripheral plasma insulin was undetectable and marked hyperglycemia, hyperlipacidemia and ketonuria prevailed, mean IRG was 624 ± 136 and 986 ±184, respectively. The highest level of IRG observed was 1450 in one dog on Day 7. These results are confirmed by using three other antiglucagon sera considered to be specific for pancreatic glucagon. We conclude that: 1) Progressively increasing amounts of material crossreacting with “specific” antiglucagon sera appear in plasma of totally depancreatized dogs fasting for up to seven days. 2) This event appears to be the consequence of metabolic derangements induced by insulin lack. 3) Hyperglucagonemia can result onoly from a defect of the pancreatic α cell, but can also be the consequence of excessive production of IRG from a nonpancreatic source. It could be that glucagon deficiency cannot be easily demmonstrated, because the release of nonpancreatic IRG can compensate for lack of pancreatic glucagon.