Decreased food intakes and body weights in rats immunized against pancreatic glucagon

Glucagon, a putative satiety peptide, has decreased food intake and antibodies to glucagon have increased food intake when administered acutely. It may be hypothesized if rats were immunized against glucagon, antibodies would chronically sequester glucagon released during meals and food intake and weight gain would increase. Female Zucker obese (n = 16, BW = 160 +/- 5 g) and lean (n = 16, BW = 123 +/- 3 g) rats were immunized against pancreatic glucagon conjugated to BSA (GG-AB) or BSA alone (BSA-AB). Only GG-AB rats developed glucagon antibody titers (p less than 0.01). During a 16 week period average daily food intakes and body weight gains were decreased 5.0 (p less than 0.001) and 9.4% (p less than 0.001) respectively in GG-AB compared with BSA-AB rats. Free glucagon, measured by RIA using a pancreatic glucagon specific antibody, was decreased 60% at 8 weeks (130 vs. 322 pg/ml, p less than 0.001) and 33% at 16 weeks (206 vs. 307 pg/ml, p less than 0.02). However, total pancreatic glucagon (free and antibody-bound) was increased 226% (428 vs. 129 pg/ml, p less than 0.02) at 16 weeks. Thus, although sufficient antibody titers were developed in rats to sequester 76% of the free circulating glucagon from both pancreatic and gut sources, food intakes and body weight gains were decreased, likely as a consequence of an over-compensatory increase in total glucagon concentrations.