| First Author | Wong HY | Year | 2021 |
| Journal | Mol Cell Endocrinol | Volume | 537 |
| Pages | 111424 | PubMed ID | 34400259 |
| Mgi Jnum | J:312970 | Mgi Id | MGI:6792554 |
| Doi | 10.1016/j.mce.2021.111424 | Citation | Wong HY, et al. (2021) The role of mitochondrial apoptotic pathway in islet amyloid-induced beta-cell death. Mol Cell Endocrinol 537:111424 |
| abstractText | Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to beta-cell death in type 2 diabetes. We previously showed that extracellular hIAPP aggregates promote Fas-mediated beta-cell apoptosis. Here, we tested if hIAPP aggregates can trigger the mitochondrial apoptotic pathway (MAP). hIAPP aggregation in Ad-hIAPP transduced INS-1 and human islet beta-cells promoted cytochrome c release, caspase-9 activation and apoptosis, which were reduced by Bax inhibitor. Amyloid formation in hIAPP-expressing mouse islets during culture increased caspase-9 activation in beta-cells. Ad-hIAPP transduced islets from Cytc(KA/KA) and BaxBak betaDKO mice (models of blocked MAP), had lower caspase-9-positive and apoptotic beta-cells than transduced wild-type islets, despite comparable amyloid formation. Blocking Fas (markedly) and Bax or caspase-9 (modestly) reduced beta-cell death induced by extracellular hIAPP aggregates. These findings suggest a role for MAP in amyloid-induced beta-cell death and a potential strategy to reduce intracellular amyloid beta-cell toxicity by blocking cytochrome c apoptotic function. |
