GLUCAGON ANTIBODIES AND AN IMMUNOASSAY FOR GLUCAGON*

Abstract

Despite extensive knowledge of the amino acid composition of beef-pork glucagon, and of the physiologic changes induced by its administration to animals and man, the role of glucagon in the homeostatic regulation of blood glucose level in normal and abnormal states remains to be defined.This fundamental gap in knowledge is the result of the lack of a method sufficiently specific and sensitive to measure endogenous glucagon in body fluids.Previous efforts to assay glucagon in plasma have been based upon ability to produce either hyperglycemia in a living animal (1-3), glycogenolysis in liver slices (4), or phosphorylase activation in liver homogenates (5).There is reason to doubt the specificity of the plasma glucagon-like activity detectable by such methods (6), and their status is at present in question.The greater specificity inherent in immunoas- says (7), coupled with the unprecedented sensi- tivity provided by the paper radiochromato-elec- trophoretic techniques of Berson and co-workers (8) suggested that a radio-immunoassay for glu- cagon might provide a hitherto unequaled range of specific measurements.In a preliminary report, the antigenicity of beef-pork glucagon in rabbits was recorded and the feasibility of a radioimmunoassay for glucagon demonstrated (9).The development by Berson and Yalow of a ra- dio-immunoassay for insulin of remarkable sensi- tivity and specificity (10, 11) has validated this approach to problems of peptide hormone assay.In the following report the antigenicity of glucagon is demonstrated, glucagon antibodies are * Supported by United States Public Health Service Grant A-2700.