GLP-1 receptor agonist attenuates endoplasmic reticulum stress-mediated β-cell damage in Akita mice.

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