Fig. 5: Ptf1a-Cre independent accumulation of Tn-modified proteins in pancreatic islets with consecutive beta cell failure.

a Assessment of Tn antigen (green) and insulin expression (red) in pancreatic sections from 4 and 40-week-old WT and Cosmc-KO fasting mice. Tn antigen expression is only observed in Cosmc-KO tissue, and Tn antigen positivity is restricted to exocrine glands in young animals, whereas prolonged Tn antigen staining is observed in islets of Langerhans in aged mice. Scale bar equals 200 µm. b Cel IHC staining of adult WT and KO tissue and IF co-staining of VVA (green) and Cel (red). Scale bar equals 200 µm. c Quantification of islets of Langerhans of WT (n = 68) and KO (n = 64) pancreata (P = 0.004). d VVA Western blot analysis of endo- and exocrine pancreatic tissue derived from WT and Cosmc-KO animals. VVA positivity is specific for KO tissue, with most of the Tn-modified proteins found in exocrine tissue. Anti-trypsin was used as an exocrine marker. e Western blot analysis of WT and Cosmc-KO endocrine tissue using anti-Cel antibody. The analysis shows that the localization of Cel is not limited to the exocrine pancreas. f VVA precipitation from endocrine WT and KO tissue lysates with WB detection using anti-Cel antibody. g Comparison of NT-3 cell viability in the presence of 20 µM CEL and CEL-Tn after 48 h shows no significant difference. h CEL-Tn shows a significant negative regulation of glucose-stimulated insulin secretion in NT-3 cells. Cells were stimulated with 25 mM glucose for 60 min in the presence of 20 µM recombinant CEL or CEL-Tn