Fas-Associated Death Receptor Signaling Evoked by Human Amylin in Islet β-Cells

• DOI: 10.2337/db07-0849
• Publication Date: 2007-11-01T00:54:28Z
• Authors: Shaoping Zhang; Hong Liu; Hua Yu; Garth J.S. Cooper
• Keywords: Fas ligand; FADD; Amylin

Aggregation of human amylin (hA) into beta-sheet-containing oligomers is linked to islet beta-cell dysfunction and the pathogenesis type 2 diabetes. Here, we investigated possible contributions Fas-associated death-receptor signaling mechanism hA-evoked apoptosis.We measured responses hA in isolated mouse islets two insulinoma cell lines, wherein Fas/Fas ligand (FasL) death domain (FADD) expression by quantitative RT-PCR, Western blotting, immunofluorescence staining. We used anti-Fas/FasL blocking antibodies Fas/FasL antagonist Kp7-6 probe roles Fas interactions regulation apoptosis hA-treated beta-cells Kp7-6-mediated effects on beta-sheet formation aggregation using circular dichroism thioflavin-T binding.hA treatment stimulated FADD beta-cells. Both suppressed but did not modify its aggregation. Therefore, receptor played a critical role induction this pathway. Interestingly, was rescued Kp7-6, which also impaired formation.This first report linking activation apoptosis. have identified antagonist, as potent inhibitor related death. These results support an interaction between surface apoptotic Increased could constitute molecular event common both 1 diabetes, although mode pathway may differ these forms