Beta-catenin is a multifunctional protein that has recently been shown to be important for the regulation of synapse formation and vesicle trafficking in neurons. PKA-induced phosphorylation of beta-catenin at ser552 increases its function by stabilising the molecule, thus allowing protein levels to increase. The gut hormone, GLP-1, is an activator of PKA, and can promote beta-catenin stability in several metabolicaly sensitive cell types. GLP-1 signalling in the brain is also important for the regulation of glucose homeostasis. The aim of the current study, therefore, was to determine if GLP-1 can signal through beta-catenin in hypothalamic neurons, and if this signal transduction pathway is involved in neurosecretion. Male rats were injected with 5μg/kg exendin4, A GLP-1 agonist, or vehicle and brains were collected for immunohistochemistry for beta-catenin. As a model for hypothalamic neurosecretary cells, GT1-7 cells, derived from the fetal hypothalamus, were treated with exendin4 and alterations in beta-catenin phosphorylation at ser552, which stabilises the molecule, and total beta-catenin levels were measured using western blot analysis, while neuroendocrine secretions were measured by EIA in supernatants after 2 hours of exendin4 incubation. Exendin4 treatment lead to increased beta-catenin stabilisation in the PVN, DMH and arcuate hypothalamic regions. Similarly, exendin4 increased b-catenin in GT1-7 cells, an effect that was PKA dependent. Furthermore, reducing beta-catenin protein expression in hypothalamic cell line with siRNA or reduced GLP-1 receptor-mediated stabilisation with the PKA inhibitor H-89, lowered GT1-7 neurosecretion. Conversly, stabilisation of beta-catenin through BIO induced GSK-3beta inhibition increased exendin4 induced neurosecretion. In conclusion our data indicate that beta catenin can be regulated by GLP-1 in hypothalamic cells, through a PKA dependent process, and this stimulation of beta-catenin by GLP-1 could enhance secretion of peptides from hypothalamic cells.