Abstract
Preproglucagon-derived peptides, among which glucagon and glucagon-like peptide-1 (GLP-1), are known to modulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis. Many effects of GPL-1, however, are preventedby its very short half-life. Hence we investigated in vivo and in vitro the effects on the rat HPA axis of the GLP-1-receptor agonist exendin-4 (EX4), which possesses a longer biological half-life than GLP-1. The bolus systemic administration of EX4 (12 nmol/kg) evoked significant rises in ACTH, aldosterone and corticosterone concentrations. EX4 (10 - 7 M) induced a weak but significant increase in corticosterone secretion from dispersed rat adrenocortical cells, and the effect was abrogated by the GLP-1-receptor antagonist exendin (9-39). Collectively, our findings indicate that EX4, acting via GLP-1 receptors, stimulates HPA axis in rats, acting on both its central (hypothalamo-pituitary) and peripheral (adrenocortical) branch.
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