Endocrine Abstracts

Aim

Glucagon stimulation test (GST) is used to assess hypothalamo-pituitary-adrenal (HPA) and GH axis with an incompletely defined mechanism. Glucagon has physiological effects on body weight and metabolic parameters and some of these effects are suggested to occur via fibroblast growth factor-21 (FGF-21) which is a circulating hepatokine. FGF-21 was also shown to affect HPA and GH axis in rodents. The aim of the present study was assess if glucagon acted through FGF-21 to stimulate the cortisol and GH secretion. Secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity.

Material and methods

A total of 26 healthy participants were included in the study. 11 participants were obese (Body Mass Index (BMI) > 30 kg/m²) and 15 had a normal weight (BMI <25 kg/m²). Basal pituitary and target hormone levels were measured and glucagon stimulation test (GST) was performed. During GST, glucose, insulin, cortisol, GH and FGF-21 responses were measured.

Results

Glucagon resulted in significant increases in FGF21, glucose, insulin, cortisol and GH levels. Serum glucose levels showed variations during GST. Peak GH and area under curve (AUC)_(GH) responses to GST in the obese group were lower than those of the normal weight group with a different pattern of response. Cortisol responses were similar in two groups. Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon. But neither cortisol nor GH response to the GST was related to FGF-21, deeper hypoglycemia may be related to increased GH response to GST in lean individuals.

Conclusion

Obesity was associated with blunted and delayed GH, but preserved cortisol responses to GST. This is the first study, at least according to our knowledge, to show that glucagon stimulates the HPA and GH axis independently from FGF21. The delayed GH response to GST in obesity does not seem to be related to FGF-21.