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GLP‐1 receptor agonist attenuates endoplasmic reticulum stress‐mediated β‐cell damage in Akita mice
Aims/Introduction: Endoplasmic reticulum (ER) stress is one of the contributing factors in the development of type 2 diabetes. To investigate the cytoprotective effect of glucagon‐like peptide 1 receptor (GLP‐1R) signaling in vivo, we examined the action of exendin‐4 (Ex‐4), a potent GLP‐1R agonist...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015545/ https://www.ncbi.nlm.nih.gov/pubmed/24843469 http://dx.doi.org/10.1111/j.2040-1124.2010.00075.x |
Sumario: | Aims/Introduction: Endoplasmic reticulum (ER) stress is one of the contributing factors in the development of type 2 diabetes. To investigate the cytoprotective effect of glucagon‐like peptide 1 receptor (GLP‐1R) signaling in vivo, we examined the action of exendin‐4 (Ex‐4), a potent GLP‐1R agonist, on β‐cell apoptosis in Akita mice, an animal model of ER stress‐mediated diabetes. Materials and Methods: Ex‐4, phosphate‐buffered saline (PBS) or phlorizin were injected intraperitoneally twice a day from 3 to 5 weeks‐of‐age. We evaluated the changes in blood glucose levels, bodyweights, and pancreatic insulin‐positive area and number of islets. The effect of Ex‐4 on the numbers of C/EBP‐homologous protein (CHOP)‐, TdT‐mediated dUTP‐biotin nick‐end labeling (TUNEL)‐ or proliferating cell nuclear antigen‐positive β‐cells were also evaluated. Results: Ex‐4 significantly reduced blood glucose levels and increased both the insulin‐positive area and the number of islets compared with PBS‐treated mice. In contrast, there was no significant difference in the insulin‐positive area between PBS‐treated mice and phlorizin‐treated mice, in which blood glucose levels were controlled similarly to those in Ex‐4‐treated mice. Furthermore, treatment of Akita mice with Ex‐4 resulted in a significant decrease in the number of CHOP‐positive β‐cells and TUNEL‐positive β‐cells, and in CHOP mRNA levels in β‐cells, but there was no significant difference between the PBS‐treated group and the phlorizin‐treated group. Proliferating cell nuclear antigen staining showed no significant difference among the three groups in proliferation of β‐cells. Conclusions: These data suggest that Ex‐4 treatment can attenuate ER stress‐mediated β‐cell damage, mainly through a reduction of apoptotic cell death that is independent of lowered blood glucose levels. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00075.x, 2010) |
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