| First Author | Wang J | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 466 |
| Issue | 3 | Pages | 300-5 |
| PubMed ID | 26361146 | Mgi Jnum | J:232872 |
| Mgi Id | MGI:5780366 | Doi | 10.1016/j.bbrc.2015.09.009 |
| Citation | Wang J, et al. (2015) The NLRP3 inflammasome is dispensable for ER stress-induced pancreatic beta-cell damage in Akita mice. Biochem Biophys Res Commun 466(3):300-5 |
| abstractText | Uncontrolled endoplasmic reticulum (ER) stress activates members of the NOD-like receptor family, which are involved in the pyrin domain containing 3 (NLRP3) inflammasome pathway. This pathway has been proposed to contribute to beta-cell dysfunction and death. However, the connection between ER stress and NLRP3 inflammasome activation remains controversial. Here we generated Akita/KO (Ins2(+/C96Y); NLRP3(-/-)) mice by crossing Akita (Ins2(+/C96Y); NLRP3(+/+)) mice with NLRP3 KO (Ins2(+/+); NLRP3(-/-)) mice. We then compared the metabolic phenotypes of the different strains. Knockout of the NLRP3 inflammasome did not affect the onset or the severity of diabetes in Akita/KO mice at any point of the study. Histological observations of pancreatic islets supported these findings. Tunicamycin-exposed islets from NLRP3 KO mice exhibited similar levels of ER stress and apoptosis induction as islets from WT (Ins2(+/+); NLRP3(+/+)) mice. Furthermore, NLRP3 deletion did not prevent tunicamycin-mediated reduction of glucose-stimulated insulin secretion. In conclusion, deletion of the NLRP3 inflammasome did not protect against ER stress-induced diabetes development or beta-cell damage, indicating that beta cell death in Akita mice is not mediated via activation of the NLRP3 inflammasome. |
