Glucagon administration elicits blunted GH but exaggerated ACTH response in obesity.
Reduction in both spontaneous and stimulated GH secretion in obesity has been clearly demonstrated. Mild hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis has been also reported. Glucagon, at least after im administration, induces clear increase in either GH or ACTH and F levels but its effect on somatotroph and corticotroph secretion in obesity has never been studied. In 7 patients with abdominal obesity (OB, aged 24-42 yr, BMI: 29.1-43.9 kg/m2, waist/hip ratio [WHR]: 0.86-1.00) we studied the GH, ACTH and F responses to the im administration of glucagon (0.017 mg/kg at 0 min). The results in OB were compared with those in a group of 6 age-matched controls normal subjects (Ns aged 26-32 yr, BMI 19.7-22.5 kg/m2). In Ns glucagon administration induced clear increase in GH (peak vs baseline, mean+/-SE: 11.6+/-3.4 vs 3.3+/-0.7 microg/l, p<0.02), and ACTH (52.9+/-15.2 vs 19.0+/-1.5 pg/ml, p<0.02) levels which peaked at +150 and +165 min, respectively. Increase in F levels (222.3+/-23.8 vs 158.3+/-7.0 ng/ml, p<0.05) was also recorded but peaked at +180 min. In OB glucagon administration induced GH response (7.4+/-2.3 vs 0.8+/-0.6 microg/l) lower (p<0.05) than that recorded in Ns; when the GH responses were evaluated by co-variance analysis, a significant difference between the 2 groups was recorded in term of peaks but not of AUCs. On the other hand, the ACTH response to glucagon in OB was higher than that in Ns (11452.6+/-2447.7 vs 4892.2+/-719.4 pg/ml x min, p<0.05). The F response to glucagon in OB and Ns was, however, similar (24057.9+/-4109.1 vs 29835.9+/-1566.0 ng/ml x min). In conclusion, this study demonstrates that in obese patients the im administration of glucagon elicits blunted GH response but exaggerated ACTH increase which is uncoupled with the adrenal response. These findings agree with the existence of concomitant GH insufficiency and altered corticotroph function in obesity.
Department of Internal Medicine, University of Turin, Italy.
F
F
Tassone
S
S
Grottoli
R
R
Rossetto
B
B
Maccagno
C
C
Gauna
R
R
Giordano
E
E
Ghigo
M
M
Maccario
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001824:Body Constitution; D015992:Body Mass Index; D005260:Female; D005934:Glucagon / Q000009:adverse effects; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D009765:Obesity / Q000503:physiopathology*
D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D006854:Hydrocortisone