Metabolic and hormonal responses to subcutaneous glucagon in healthy beagles

Objective - To compare the effects of subcutaneous (SC) and intravenous (IV) glucagon on glucose concentrations, and insulin and cortisol secretion. Design - Prospective randomized 3-way crossover study. Setting - University teaching hospital. Animals - Five healthy beagles. Interventions - Diabetes mellitus and adrenal insufficiency were excluded by repeated glucose and fructosamine measurements, urinalysis, abdominal ultrasonography, and ACTH stimulation tests. Blood samples were collected before and after the SC and IV injection of 1 milligram (1 mg = 1 mL) commercially available synthetic glucagon and analyzed for insulin-like immunoreactivity (insulin-imr), glucose, ACTH and cortisol concentrations. The results were compared with those obtained after the SC injection of 1 mL saline (placebo). Measurements were performed over a period of up to 3 hours. Measurements and Main Results - SC glucagon significantly increased glucose and insulin-imr (P < 0.001 and 0.043, respectively). Peak glucose concentrations were observed after 20 minutes and were lower than after IV injection (mean +/- SD: 6.5 +/- 1.1 mmol/L versus 9.3 +/- 0.8 mmol/L [117.1 +/- 19.8 mg/dL versus 167.6 +/- 14.4 mg/dL]; P = 0.001). The route of application had no significant effect on insulin-imr (peak concentration: median [range]: 83.3 [13.9312.5] pmol/L versus 194.5 [118.1284.7] pmol/L [12 [245] mu U/mL versus 28 [1741] mu U/mL; P = 0.151). SC glucagon did not increase cortisol or ACTH concentrations at any time point of observation (P > 0.05). Aside from somnolence, no adverse events were recorded. Conclusions - SC glucagon has the potential to be used as a simple and safe test in diabetic animals, but is of little use in animals with suspected corticotrophic insufficiency. The hyperglycemic effects are significant, implying that the commercially available human emergency kit could be useful in the home treatment of canine hypoglycemic emergencies.