Current studentsExisting staffContact us
 

Feeding and glucagon-like peptide-1 receptor activation stabilise β-catenin in specific hypothalamic nuclei in male rats

Simple item page
dc.contributor.authorMcEwen, H.J.L.
dc.contributor.authorCognard, E.
dc.contributor.authorLadyman, S.R.
dc.contributor.authorKhant Aung, Z.
dc.contributor.authorTups, A.
dc.contributor.authorShepherd, P.R.
dc.contributor.authorGrattan, D.R.
dc.date.issued2018
dc.description.abstractβ-catenin is a multifunctional protein that not only acts in the canonical Wnt/β-catenin pathway to regulate gene expression but also binds to cadherin proteins in adherens junctions, where it plays a key role in regulating cytoskeleton linked with these junctions. Recently, evidence has been presented indicating an essential role for β-catenin in regulating the trafficking of insulin vesicles in β-cells and showing that changes in nutrient levels rapidly alter levels of β-catenin in these cells. Given the importance of neuroendocrine hormone secretion in the regulation of whole body glucose homeostasis, the present study aimed to investigate whether β-catenin signalling is regulated in the hypothalamus during the normal physiological response to food intake. Rats were subjected to a fasting/re-feeding paradigm, and then samples were collected at specific timepoints for analysis of β-catenin expression by immunohistochemistry and western blotting. Changes in gene expression were assessed by a quantitative reverse transcriptase-polymerase chain reaction. Using immunohistochemistry, feeding acutely increased detectable cytoplasmic levels of β-catenin (‘stabilised β-catenin’) in neurones in specific regions of the hypothalamus involved in metabolic regulation, including the arcuate, dorsomedial and paraventricular nuclei of the hypothalamus. Feeding-induced elevations in β-catenin in these nuclei were associated with an increased transcription of several genes known to be responsive to Wnt/β-catenin signalling. The effect of feeding was mimicked by administration of the GLP-1 agonist exendin-4 and was also characterised by cAMP-dependent phosphorylation of β-catenin at serine residues 552 and 675. These data suggest that β-catenin/T cell factor signalling is involved in metabolic sensing in the hypothalamus.
dc.identifier.citationJournal of Neuroendocrinology, 2018; 30(6):1-10
dc.identifier.doi10.1111/jne.12607
dc.identifier.issn0953-8194
dc.identifier.issn1365-2826
dc.identifier.urihttps://hdl.handle.net/11541.2/137791
dc.language.isoen
dc.publisherWiley
dc.relation.fundingHealth Research Council of New Zealand
dc.relation.fundingMaurice Wilkins Centre for Molecular Biodiscovery
dc.rightsCopyright 2018 British Society for Neuroendocrinology
dc.source.urihttps://doi.org/10.1111/jne.12607
dc.subjectarcuate nucleus
dc.subjectglucose homeostasis
dc.subjecthypothalamus
dc.subjectWnt/beta-catenin
dc.titleFeeding and glucagon-like peptide-1 receptor activation stabilise β-catenin in specific hypothalamic nuclei in male rats
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916296911601831

Files

Collections