GLP-1 agonists enhance stress-induced corticosterone release
V. Volke1,2, K. Rünkorg2 & M. Krass2
Introduction: Currently, there are two glucagon-like peptide 1 (GLP-1) receptor agonists approved for the treatment of type 2 diabetes.
While the primary pharmacological actions of GLP-1 agonists are antihyperglycaemic effect and weight reduction, these drugs may influence other neural and hormonal processes. Animal studies have indicated that GLP-1 receptors are involved in the regulation of stress, anxiety, learning and memory as well as regulation of corticosterone and aldosterone release.
Objective: The aim of the current study was to compare the behavioural and hormonal effects of glucaemically equipotent doses of exenatide and liraglutide in mice after acute and chronic treatment.
Methods: The effects of GLP-1 receptor agonists were determined on anxiety level in the light-dark compartment test, the motor activity in automated activity cages and finally, the forced swimming test (used to detect antidepressant-like effects) was performed. The plasma levels of corticosterone and aldosterone were also measured.
Results: Both exenatide (120 μg/kg s.c.) and liraglutide (200-1200 μg/kg s.c.) induced very similar behavioural and hormonal effects after acute administration: there was no change on anxiety level or immobility time, however, both drugs dose dependently suppressed motor activity. Remarkably, GLP-1 agonists stimulated corticosterone release even when combined with the swimming stress. After chronic dosing of GLP-1 agonists (exenatide 10 μg/kg bid; liraglutide 1200 μg/kg qd for 2 weeks) both drugs still enhanced stress-induced corticosterone release but did not change the locomotion of animals. The effects on aldosterone levels are also reported.
Conclusion: We conclude that exenatide and liraglutide induce very similar suppression of motor activity and stimulation of corticosterone release in mice. Interestingly, tolerance developed to hypolocomotory effect but not to corticosterone stimulating effect of GLP-1 agonists during 2 weeks of treatment.
Effect of chronic treatment with exenatide and liraglutide on plasma corticosterone Results are expressed as mean ±S.E.M. n=910. *P<0.05 vs. saline (Newman-Keuls test)
Declaration of interest: I fully declare a conflict of interest. Details below:
Funding: This work was supported, however funding details unavailable.