Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats

  • Authors:
    • Ludwik K. Malendowicz
    • Giuliano Neri
    • Gastone G. Nussdorfer
    • Krzysztof W. Nowak
    • Agnieszka Zyterska
    • Agnieszka Ziolkowska
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijmm.12.4.593
  • Pages: 593-596
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Evidence is available that exendin-4 (EX4), a glucagon-like peptide-1 receptor (GLP-1R) agonist acutely stimulates hypothalamo-pituitary-adrenal (HPA) axis in the rat. EX4 is a potent insulinotropic agent, which is currently under clinical trial for treatment of type 2 diabetes. Since diabetes is known to affect adrenal function, we investigated the effects of the prolonged administration of EX4 and/or the GLP-1R antagonist EX4(9-39) (EX4-A) (daily subcutaneous injections of 1 nmol/kg EX4 and/or EX4-A, for 7 days) on the HPA axis of normoglycemic and streptozotocin (STZ)-induced diabetic rats. In STZ-untreated rats, chronic EX4 treatment did not change the blood level of ACTH. In contrast, it evoked a marked rise in the plasma concentrations of aldosterone and corticosterone, these effects being reversed by EX4-A. In STZ-induced diabetic rats, prolonged EX4 administration increased the plasma levels of ACTH, aldosterone and corticosterone. EX4-A did not prevent the first two effects of EX4, and annulled the latter one. These findings allow us to draw the following conclusions: i) EX4 prolonged exposure desensitizes hypothalamo-hypophyseal GLP-1R in normal rats, and exerts an ACTH-independent GLP-1R-mediated aldosterone and corticosterone secretagogue effect; and ii) experimental diabetes induces the expression of EX4 receptors other than the classic GLP-1R, whose activation mediate the ACTH and aldosterone, but not corticosterone, secretagogue effects. Our study provides evidence that metabolic dysregulations occurring in STZ-induced diabetic rats are able to profoundly affect the response of the HPA axis to GLP-1.

Related Articles

Journal Cover

October 2003
Volume 12 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Malendowicz LK, Neri G, Nussdorfer GG, Nowak KW, Zyterska A and Ziolkowska A: Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats. Int J Mol Med 12: 593-596, 2003.
APA
Malendowicz, L.K., Neri, G., Nussdorfer, G.G., Nowak, K.W., Zyterska, A., & Ziolkowska, A. (2003). Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats. International Journal of Molecular Medicine, 12, 593-596. https://doi.org/10.3892/ijmm.12.4.593
MLA
Malendowicz, L. K., Neri, G., Nussdorfer, G. G., Nowak, K. W., Zyterska, A., Ziolkowska, A."Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats". International Journal of Molecular Medicine 12.4 (2003): 593-596.
Chicago
Malendowicz, L. K., Neri, G., Nussdorfer, G. G., Nowak, K. W., Zyterska, A., Ziolkowska, A."Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats". International Journal of Molecular Medicine 12, no. 4 (2003): 593-596. https://doi.org/10.3892/ijmm.12.4.593