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- Title
Asymmetric dimethylation and citrullination in the LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, and effects of anti-TCR/anti-TNF-α antibody-based therapy.
- Authors
Bollenbach, Alexander; Tsikas, Dimitrios; Lenzen, Sigurd; Jörns, Anne
- Abstract
The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D). We determined by GC–MS the extent of asymmetric dimethylation (prADMA) and citrullination (prCit) of l-arginine residues in organ proteins (pr) of normoglycaemic control (ngCo, n = 6), acutely diabetic (acT1D, n = 6), chronically diabetic (chT1D, n = 4), and cured (cuT1D, n = 4) rats after anti-TCR/anti-TNF-α therapy. Pancreatic prCit and prADMA did not differ between the groups but were correlated (r = 0.728, P = 0.0003, n = 20). acT1D rats had lower prCit levels in spleen and kidney than ngCo rats. cuT1D rats had higher prADMA levels than chT1D rats only in the spleen. Combination therapy re-established normoglycaemia and increased prADMA in the spleen without altering pancreatic prADMA and prCit. Western blotting demonstrated the presence of different prADMA pattern, especially an ≈ 50-kDa prADMA in spleen and pancreas, and an ≈ 25-kDa prADMA in the pancreas only, with the kidney showing only a very faint and small prADMA. Besides the changes in the pancreas during different metabolic states, the spleen may play a stronger role for the recognition of metabolic changes in T1D than thought thus far.
- Subjects
TYPE 1 diabetes; ASYMMETRIC dimethylarginine; ANIMAL models in research; RATS; WESTERN immunoblotting; SPLEEN
- Publication
Amino Acids, 2020, Vol 52, Issue 1, p103
- ISSN
0939-4451
- Publication type
Article
- DOI
10.1007/s00726-019-02811-5