دورية أكاديمية
Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells
| العنوان: | Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells |
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| المؤلفون: | Vieira, Elaine, Marroquí, Laura, Figueroa, Ana Lucia, Merino, Beatriz, Fernandez-Ruiz, Rebeca, Nadal, Angel, Burris, Thomas P., Gomis, Ramon, 1946-, Quesada, Ivan |
| المصدر: | Articles publicats en revistes (Medicina) |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2013 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Glucosa, Citoquines, Genètica humana, Pàncrees, Glucose, Cytokines, Human genetics, Pancreas |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 15 p.; application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0069939Test; PLoS One, 2013, vol. 8, num. 7, p. e69939; https://doi.org/10.1371/journal.pone.0069939Test; http://hdl.handle.net/2445/124881Test; 632142 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0069939Test http://hdl.handle.net/2445/124881Test |
| حقوق: | cc-by (c) Vieira, Elaine et al., 2013 ; http://creativecommons.org/licenses/by/3.0/esTest ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BA3CFBD6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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