An immunohistochemical study of nitrotyrosine expression in pancreatic islets of cases with increasing duration of type 1 diabetes and without diabetes.
Peroxynitrite-induced nitration of cellular proteins has been shown to associate with various human pathologies. The expression of pancreatic nitrotyrosine and its cellular source relative to insulitis were analysed in cases with increasing duration of type 1 diabetes and compared with non-diabetic autoantibody-negative and -positive cases. Pancreatic tail sections from non-diabetic autoantibody-negative cases (Group 1; n = 7), non-diabetic autoantibody-positive cases (Group 2; n = 6), recently diagnosed cases (Group 3; n = 6), 0.25-5 years of diabetes (Group 4; n = 8) and 7-12 years of diabetes (Group 5; n = 6) were immunostained sequentially for nitrotyrosine, insulin and leucocytes. Nitrotyrosine expression was observed in selective beta cells only. In group 1, the percentage of insulin-positive islets with nitrotyrosine ranged from 7.6 to 58.8%. In group 2, it was minimally expressed in 2 cases and was present in 4.7-19.3% of insulin-positive islets in 3 cases and in all islets in 1 case. In group 3, it was absent in 1 case and in the remaining 5 cases, the values were 17.4-85.7%. In group 4, nitrotyrosine was absent in 6 cases and positive in 1.8 and 22.2% of insulin-positive islets in 2 cases. In group 5, the values were 60% (1 case) and 100% (2 cases), being absent in 3 cases, consistent with insulin-negativity. This case analysis shows that nitrotyrosine immunostaining is independent of the presence and severity of insulitis. Variable nitrotyrosine expression is present in some non-diabetic cases. Its increased expression in beta cells of recent-onset and long-standing disease requires further studies to determine whether beta cell nitration plays a pathogenic role during T1D.
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Charlton
C
Martin
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
Lars
L
Krogvold
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Shebani
S
Farik
Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Satya
S
Amirapu
Diabetes Unit, Auckland District Health Board, Auckland, New Zealand.
Fiona
F
Wu
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. s.reddy@auckland.ac.nz.
Shiva
S
Reddy
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
Knut
K
Dahl-Jørgensen
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D055815:Young Adult
C002744:3-nitrotyrosine; D014443:Tyrosine
Beta cells; Human type 1 diabetes; Islets; Nitrosative stress; Nitrotyrosine