Abstract:
BACKGROUND:The potential benefits of islet xenografting in type 1 diabetes include the intriguing, but still unanswered, possibility that the grafted xenoislets may be less subjected to human autoimmune attack. Cytokines may play a major role in the pathogenesis of autoimmune diabetes by causing impairment of insulin release and pancreatic islet cell toxicity. METHODS:We compared insulin secretion, islet cell death and survival, inducible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1,000 U/ml recombinant human tumor necrosis factor-alpha and 1,000 U/ml recombinant human interferon-gamma. RESULTS:After 24-hr exposure, a marked decrease of glucose-stimulated insulin secretion was observed with human, but not with bovine islets. After 48-hr exposure, human, but not bovine, pancreatic islets showed a significantly higher percentage of apoptotic cells compared to controls. Treatment of human islets with human cytokines induced up-regulation of iNOS mRNA, increased levels of nitrites, and down-regulation of Bcl-2 mRNA, with unchanged levels of Bax mRNA. These parameters were not affected by cytokines in bovine islets. CONCLUSIONS:Bovine islets are less susceptible than human islets to the effects of human cytokines, which may be a potential advantage of xenotransplantation.
journal_name
Transplantationjournal_title
Transplantationauthors
Piro S,Lupi R,Dotta F,Patanè G,Rabuazzo MA,Marselli L,Santangelo C,Realacci M,Del Guerra S,Purrello F,Marchetti Pdoi
10.1097/00007890-200101150-00004subject
Has Abstractpub_date
2001-01-15 00:00:00pages
21-6issue
1eissn
0041-1337issn
1534-6080journal_volume
71pub_type
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