Different sensitivity to the cytotoxic action of IAPP fibrils in two insulin-producing cell lines, HIT-T15 and RINm5F cells.

We studied whether fibrils spontaneously formed by islet amyloid polypeptide (IAPP, also designated amylin) are cytotoxic to insulin producing cells by examining two different insulin producing cell lines, HIT-T15 and RINm5F. IAPP fibrils (</=10microM) added to HIT-T15 cells for one week did not diminish cell viability (tetrazolium bioreduction) or DNA synthesis (3H-thymidine incorporation) nor did it increase cell death (trypan blue staining) or degree of apoptosis (TUNEL assay), and glucose-stimulated insulin secretion and the cytosolic concentration of Ca2+ were unaffected. Similarly, control fibrils (Alzheimer's peptide, Abeta1-42, fibrils) did not reduce cellular function. In contrast, IAPP fibrils decreased cell viability (tetrazolium bioreduction) and increased number of apoptotic cells in RINm5F cells. Furthermore, hydrogen peroxide markedly impaired tetrazolium bioreduction in RINm5F cells but not in HIT-T15 cells. Glutathione reductase activity was increased by IAPP fibrils in RINm5F cells but not in HIT-T15 cells. Our data suggest a different sensitivity for the cytotoxic action of IAPP fibrils between RINm5F and HIT-T15 cells, which may be ascribed to different sensitivity to formation and action of oxygen intermediates.