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DC Field | Value | Language |
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dc.contributor.author | Vieira, Elaine | - |
dc.contributor.author | Marroquí, Laura | - |
dc.contributor.author | Figueroa, Ana Lucia | - |
dc.contributor.author | Merino, Beatriz | - |
dc.contributor.author | Fernandez-Ruiz, Rebeca | - |
dc.contributor.author | Nadal, Angel | - |
dc.contributor.author | Burris, Thomas P. | - |
dc.contributor.author | Gomis, Ramon, 1946- | - |
dc.contributor.author | Quesada, Ivan | - |
dc.date.accessioned | 2018-09-27T13:41:13Z | - |
dc.date.available | 2018-09-27T13:41:13Z | - |
dc.date.issued | 2013-07-25 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/124881 | - |
dc.description.abstract | Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60-70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0069939 | - |
dc.relation.ispartof | PLoS One, 2013, vol. 8, num. 7, p. e69939 | - |
dc.relation.uri | https://doi.org/10.1371/journal.pone.0069939 | - |
dc.rights | cc-by (c) Vieira, Elaine et al., 2013 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Glucosa | - |
dc.subject.classification | Citoquines | - |
dc.subject.classification | Genètica humana | - |
dc.subject.classification | Pàncrees | - |
dc.subject.other | Glucose | - |
dc.subject.other | Cytokines | - |
dc.subject.other | Human genetics | - |
dc.subject.other | Pancreas | - |
dc.title | Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 632142 | - |
dc.date.updated | 2018-09-27T13:41:13Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 23936124 | - |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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632142.pdf | 2.15 MB | Adobe PDF | View/Open |
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