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Sensitivity of human pancreatic islets to peroxynitrite‐induced cell dysfunction and death
Author(s) -
Delaney Carol A.,
Tyrberg Björn,
Bouwens Luc,
Vaghef Hamid,
Hellman Björn,
Eizirik Décio L.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00977-5
Subject(s) - peroxynitrite , pancreatic islets , islet , medicine , programmed cell death , chemistry , sensitivity (control systems) , endocrinology , diabetes mellitus , apoptosis , biochemistry , enzyme , electronic engineering , engineering , superoxide
Nitric oxide and peroxynitrite (generated by the reaction of nitric oxide with the superoxide anion) may both be mediators of β‐cell damage in early insulin‐dependent diabetes mellitus. We observed that acute exposure of primary cultured human pancreatic islets to peroxynitrite results in a significant decrease in glucose oxidation and islet retrieval. DNA strand breaks in single human and rat islet cells are detectable after acute peroxynitrite exposure, followed by a decrease in islet cell survival after 1 h and 24 h. Cell death appeared to occur via a toxic cell death mechanism (necrosis) rather than apoptosis, as suggested by vital staining and ultrastructural evidence of early membrane and organelle degradation, mitochondrial swelling and loss of matrix. This study demonstrates for the first time that cultured human pancreatic islets are susceptible to the noxious effects of peroxynitrite.