Persistent pancreatic glucagon but not insulin response to arginine in pancreatectomized dogs.

Effects of total pancreatectomy on plasma glucagon, insulin and glucose responses to arginine were determined in 5 dogs. Portal vein and femoral artery samples were obtained in response to an arginine infusion (10 g/30 min) prior to, 1 h, 1 day and 1 week after pancreatectomy. Glucagon was measured using pancreatic-specific antiserum 30K (Unger, Dallas). Before pancreatectomy arginine significantly increased portal vein glucagon from 373 plus or minus 36 to 595 plus or minus 31 pg/ml and femoral artery levels from 233 plus or minus 28 to 342 plus or minus 74 pg/ml. Portal vein and femoral artery insulin concentrations of 74 plus or minus 21 and 17 plus or minus 3 muU/ml increased significantly to 173 plus or minus 64 and 31 plus or minus 7 muU/ml. Glucose levels did not change. One h after pancreatectomy, portal vein glucagon decreased to 121 plus or minus 15 pg/ml but increased to 230 plus or minus 42 pg/ml after arginine. Elevated blood glucose and the necessity for insulin treatment established the adequacy of pancreatectomy. Furthermore portal vein insulin levels were undetectable and unresponsive to arginine or a combination of glucose, glucagon, and tolbutamide 1 week after pancreatectomy. One day after pancreatectomy arginine significantly increased portal vein glucagon from 343 plus or minus 42 to 776 plus or minus 152 pg/ml. One week after pancreatectomy basal glucagon values were 374 plus or minus 30 in the portal vein and 360 plus or minus 49 in the femoral artery and responded to 1226 plus or minus 641 and 825 plus or minus 270 pg/ml, respectively, with arginine. Chromatography of plasma from one pancreatectomized dog on Sephadex G-50 after arginine stimulation revealed that much of the material cross-reacting with antibody 30K was eluted from the column earlier than either 125I-insulin or 125I-glucagon. In contrast, peak glucagon activity in plasma obtained from a normal human given arginine eluted from the column between the peak of 125I-insulin and 125I-glucagon; glucagon added to human plasma also was recovered in this same area between the 125I-insulin and 125I-glucagon peaks. These results suggest that some of the material that reacted with 30K antibody and which increased after pancreatectomy in response to arginine has a molecular weight greater than pancreatic glucagon. At autopsy no pancreatic tissue could be identified. Thus, after pancreatectomy, validated by absent insulin responses, the glucagon response to arginine was normal or increased. Since arginine is not thought to increase intestinal glucagon-like immunoreactive material, the source and nature of the material measured as glucagon after pancreatectomy is unknown, but may be important to any understanding of plasma glucagon measurements.