Duration of fasting but not diurnal variation affects the response to glucagon in healthy cats

• A novel protocol for glucagon stimulation test using human-recombinant glucagon is described.
• All intravenous doses of human-recombinant glucagon resulted in occasional vomiting and nausea.
• A 20 mcg/kg intramuscular dose was eventually chosen for further study.
• The effect of diurnal variation and duration of fasting on the response to glucagon was assessed in 5 healthy cats in a repeated-measure study.
• Prolonged fasting significantly blunted the glycemic response to glucagon compared with shorter fasting.
• Diurnal variation had no significant effect on glucose or insulin responses to glucagon.

The role of glucagon disturbances in diabetes is increasingly recognized. Glucagon stimulation tests (GSTs) have been described in cats previously, but information is lacking on the response of cats to glucagon under specific conditions. The aim of this study was to assess a novel protocol for GST using human-recombinant glucagon and the effect of diurnal variation and duration of fasting using this protocol in healthy cats. All intravenous doses resulted in occasional vomiting and nausea, and eventually, a 20-μg/kg intramuscular dose was chosen. Five healthy cats were then used in a repeated-measures study. Cats were free-fed regularly at 7:30 AM and 5:30 PM for 30 min. In each cat, GST was performed at 7 PM after a 25-h fast (PM25), at 9 AM after a 25-h fast (AM25), and at 9 AM after a 15-h fast (AM15). Glucose and insulin concentrations were measured at −15, 0, 15, 25, 35, 45, and 60 min after stimulation. Baseline and peak concentrations were compared using the Friedman test. Baseline glucose and insulin did not differ significantly between treatment groups. Peak glucose concentrations occurred at 15 min and were significantly higher (P = 0.0085) at AM15 (mean ± standard deviation = 185.2 ± 43.0 mg/dL) vs AM25 (144.4 ± 10.5 mg/dL) and PM25 (128.0 ± 18.4 mg/dL). Similarly, peak insulin concentrations occurred at 15 min and were significantly higher (P = 0.04) at AM15 (1,911 ± 1,153 pg/mL) vs AM25 (739 ± 52 pg/mL) or PM25 (549 ± 366 pg/mL). In conclusion, prolonged fasting significantly blunted the glycemic response to glucagon compared with shorter fasting, but diurnal variation had no significant effect on glucose or insulin responses.