Neutralization of Endogenous Glucagon by High Titer Glucagon Antiserum

Immunization of rabbits and guinea pigs with glucagon conjugated to Limulus hemocyanin using the bifunctional imidoester diethylmalonimidate as the coupling agent resulted in the production of high titered glucagon antiserum. The production of acute glucagon deficiency in the fasted rat by the intravenous injection of glucagon antiserum resulted in significant hypoglycemia. This is the first demonstration of a biologic effect of acute glucagon deficiency and supports the contention that glucagon plays an important regulatory role in the maintenance of euglycemia in the starved rat. Similar effects were not noted in fed rats, suggesting that the hormone does not have a comparable gluco-regulatory function in the fed rat. Glucagon antibodies also inhibited the lipolytic effects of the hormone on the isolated rat epididymal fat cell. The ability to induce a specific and isolated deficiency of glucagon in the intact animal should permit elucidation of the physiological role of the hormone in the maintenance of metabolic homeostasis. (Endocrinology86: 1383, 1970)