GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation
dc.contributor.author | Carlessi, Rodrigo Maron | pt_BR |
dc.contributor.author | Chen, Younan | pt_BR |
dc.contributor.author | Rowlands, Jordan | pt_BR |
dc.contributor.author | Cruzat, Vinicius Fernandes | pt_BR |
dc.contributor.author | Keane, Kevin Noel | pt_BR |
dc.contributor.author | Egan, Lauren | pt_BR |
dc.contributor.author | Mamotte, Cyril | pt_BR |
dc.contributor.author | Stokes, Rebecca | pt_BR |
dc.contributor.author | Gunton, Jenny E. | pt_BR |
dc.contributor.author | Bittencourt Junior, Paulo Ivo Homem de | pt_BR |
dc.contributor.author | Newsholme, Philip | pt_BR |
dc.date.accessioned | 2021-08-11T04:48:20Z | pt_BR |
dc.date.issued | 2016 | pt_BR |
dc.identifier.issn | 2045-2322 | pt_BR |
dc.identifier.uri | http://hdl.handle.net/10183/225545 | pt_BR |
dc.description.abstract | Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18hours promotes metabolic reprogramming of β-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of HypoxiaInducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression. | en |
dc.format.mimetype | application/pdf | pt_BR |
dc.language.iso | eng | pt_BR |
dc.relation.ispartof | Scientific reports. London. Vol. 7, article 2661, 13 p. | pt_BR |
dc.rights | Open Access | en |
dc.subject | Peptídeo 1 semelhante ao glucagón | pt_BR |
dc.subject | Hormone receptors | en |
dc.subject | Receptor do peptídeo semelhante ao glucagon 1 | pt_BR |
dc.subject | Type 2 diabetes | en |
dc.subject | Diabetes mellitus tipo 2 | pt_BR |
dc.title | GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation | pt_BR |
dc.type | Artigo de periódico | pt_BR |
dc.identifier.nrb | 001023504 | pt_BR |
dc.type.origin | Estrangeiro | pt_BR |
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