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The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21

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Abstract

Purpose

Glucagon stimulation test (GST) is used to assess the hypothalamo-pituitary-adrenal (HPA) and growth hormone (GH) axes with an incompletely defined mechanism. We aimed to assess if glucagon acted through fibroblast growth factor-21 (FGF-21) to stimulate cortisol and GH secretion. The secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity.

Methods:

A total of 26 healthy participants; 11 obese (body mass index (BMI) > 30 kg/m2) and 15 leans (BMI < 25 kg/m2) were included. Basal pituitary and target hormone levels were measured and GST was performed. During GST, glucose, insulin, cortisol, GH, and FGF-21 responses were measured.

Results:

The mean age of the participants was 26.3±3.6 years. Glucagon resulted in significant increases in FGF-21, glucose, insulin, cortisol, and GH levels. The levels of basal cortisol, GH, FGF-21, and IGF-1 were similar in the two groups. The peak GH and area under the 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. There were no differences between the groups in terms of peak cortisol, AUC(cortisol), peak insulin, AUC(insulin), peak FGF-21, and AUC(FGF21). Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon.

Conclusion

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

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was funded by the Scientific Research Unit of the Erciyes University, under the project number TTU-2019-9216.

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Authors and Affiliations

  1. Erciyes University Medical School Department of Endocrinology, Kayseri, Turkey

    Ilyas Akkar, Zuleyha Karaca, Kursad Unluhizarci & Aysa Hacioglu

  2. Erciyes University Medical School Department of Medical Biology, Kayseri, Turkey

    Serpil Taheri

  3. Yeditepe University Medical School Department of Endocrinology, Istanbul, Turkey

    Fahrettin Kelestimur

Authors
  1. Ilyas Akkar
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  2. Zuleyha Karaca
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  3. Serpil Taheri
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  4. Kursad Unluhizarci
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  5. Aysa Hacioglu
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  6. Fahrettin Kelestimur
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Corresponding author

Correspondence to Zuleyha Karaca.

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The authors declare no competing interest.

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Informed consent was obtained from all individual participants included in the study.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Erciyes University Medical Faculty (2019 / 263).

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Akkar, I., Karaca, Z., Taheri, S. et al. The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21. Endocrine 75, 211–218 (2022). https://doi.org/10.1007/s12020-021-02829-4

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  • DOI: https://doi.org/10.1007/s12020-021-02829-4

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