It is widely accepted that glucagon stimulates GH, ACTH and cortisol release in humans, though the mechanisms underlying these effects are unclear. Aim of the present study was to evaluate the stimulatory effect of intramuscolar (i.m.) and intravenous (i.v.) glucagon (GLU) administration on ACTH, cortisol (F) and GH release in normal adult subjects and to compare its effect on hypothalamo-pituitary adrenal (HPA) axis with that of hCRH. To this goal, in 6 normal young women (26-32 yrs, 50-58 kg) we studied the ACTH and F responses to either i.m. or i.v. GLU (1 mg, approximately 0.017 mg/kg in subjects of 54.1 +/- 1.6 kg) administration as well as to i.v. hCRH (2.0 micrograms/kg) or placebo administration. The GH and glucose variations after GLU administration were also studied. I.v. GLU did not modify the spontaneous decrease of ACTH and cortisol levels observed after placebo. Conversely, i.m. GLU elicited clear-cut ACTH and F responses (peak vs baseline, mean +/- SEM: 53.0 +/- 15.2 vs 19.0 +/- 1.5 pg/ml, p < 0.05 and 222.3 +/- 23.8 vs 158.3 +/- 7.0 micrograms/l, p < 0.05) which were higher than those recorded after hCRH (28.1 +/- 4.6 vs 17.4 +/- 3.1 pg/ml, p < 0.02 and 182.7 +/- 22.8 vs 114.8 +/- 12.3 micrograms/l p < 0.02), though this difference did not attain statistical significance. Also GH rise was recorded after i.m. but not after i.v. GLU administration (11.6 +/- 3.4 vs 3.3 +/- 0.7 micrograms/l, p < 0.05). Thirty min after both i.v. and i.m. GLU administration glucose levels showed a similar increase followed by similar decrease. The intramuscular administration of GLU induced negligible side-effects in some subject (mild and transient nausea) which, on the contrary, were clear in all subjects after its intravenous administration (nausea, vomiting, tachycardia). In conclusion, glucagon 'per se' is not an ACTH, cortisol and GH secretagogue. After intramuscular administration glucagon is a stimulus of HPA axis at least as effective as hCRH. The mechanisms underlying the ACTH, cortisol and GH responses to i.m. glucagon unlikely include glucose variations or stress.
Glucagon is an ACTH secretagogue as effective as hCRH after intramuscolar administration while it is ineffective when given intravenously in normal subjects.
ARVAT, Emanuela;GIORDANO, Roberta;BROGLIO, Fabio;MACCARIO, Mauro;CAMANNI, Franco;GHIGO, Ezio
2000-01-01
Abstract
It is widely accepted that glucagon stimulates GH, ACTH and cortisol release in humans, though the mechanisms underlying these effects are unclear. Aim of the present study was to evaluate the stimulatory effect of intramuscolar (i.m.) and intravenous (i.v.) glucagon (GLU) administration on ACTH, cortisol (F) and GH release in normal adult subjects and to compare its effect on hypothalamo-pituitary adrenal (HPA) axis with that of hCRH. To this goal, in 6 normal young women (26-32 yrs, 50-58 kg) we studied the ACTH and F responses to either i.m. or i.v. GLU (1 mg, approximately 0.017 mg/kg in subjects of 54.1 +/- 1.6 kg) administration as well as to i.v. hCRH (2.0 micrograms/kg) or placebo administration. The GH and glucose variations after GLU administration were also studied. I.v. GLU did not modify the spontaneous decrease of ACTH and cortisol levels observed after placebo. Conversely, i.m. GLU elicited clear-cut ACTH and F responses (peak vs baseline, mean +/- SEM: 53.0 +/- 15.2 vs 19.0 +/- 1.5 pg/ml, p < 0.05 and 222.3 +/- 23.8 vs 158.3 +/- 7.0 micrograms/l, p < 0.05) which were higher than those recorded after hCRH (28.1 +/- 4.6 vs 17.4 +/- 3.1 pg/ml, p < 0.02 and 182.7 +/- 22.8 vs 114.8 +/- 12.3 micrograms/l p < 0.02), though this difference did not attain statistical significance. Also GH rise was recorded after i.m. but not after i.v. GLU administration (11.6 +/- 3.4 vs 3.3 +/- 0.7 micrograms/l, p < 0.05). Thirty min after both i.v. and i.m. GLU administration glucose levels showed a similar increase followed by similar decrease. The intramuscular administration of GLU induced negligible side-effects in some subject (mild and transient nausea) which, on the contrary, were clear in all subjects after its intravenous administration (nausea, vomiting, tachycardia). In conclusion, glucagon 'per se' is not an ACTH, cortisol and GH secretagogue. After intramuscular administration glucagon is a stimulus of HPA axis at least as effective as hCRH. The mechanisms underlying the ACTH, cortisol and GH responses to i.m. glucagon unlikely include glucose variations or stress.
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