A Study of the Physiological Role of Glucagon Passive Immunization with Antiserum Specific for Pancreatic Glucagon in Rats

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Abstract
To investigate the physiological role of glucagon in the maintenance of euglycemia, the effect of the neutralization of glucagon by an antiserum specific for glucagon on blood glucose and C-peptide immunoreactivity (CPR) levels was studied in theb asal as well as in the hyperglucagonemic states caused by hypoglycemia or an intravenous infusion of arginine in rats. The antiserum employed in this study was raised in rabbits by subcutaneous injection of a conjugate of BSAand the C-terminal fragment of glucagon. Since the antiserum was found to contain 896 ng/ml of antibody-bound glucagon, the antigen-stripped glucagon antibody was prepared. Its affinity constant and binding capacity were 2.57×1010 M-1 and 147 nM, respectively. After the administration of 1 ml of the antiserum in 24-hr-fasted rats, no free immuno reactive glucagon (IRG) was detected during the experiment for 60 min. Likewise, antiserum treatment prevented a rise in the plasma IRG level following an arginine infusion and insulin-induced hypoglycemia. Plasma CPR levels tended to be lower in antiserum-treated rats than in the control in any conditions covered by the present study. However, changes in blood glucoselevels the both groups were comparable. These results demonstrate that in the presence of glucagon antibodids euglycemia can be maintained with a reduced supply of insulin.

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