Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Amino Acids. 2020 Jan;52(1):103-110. doi: 10.1007/s00726-019-02811-5. Epub 2019 Dec 12.
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.
LEW.1AR1-iddm 大鼠是人类 1 型糖尿病（T1D）的动物模型。我们通过 GC-MS 测定了正常血糖对照（ngCo，n=6）、急性糖尿病（acT1D，n=6）、慢性糖尿病（chT1D，n=4）和治愈（cuT1D，n=4）大鼠器官蛋白（pr）中 L-精氨酸残基的不对称二甲基化（prADMA）和瓜氨酸化（prCit）程度。胰腺 prCit 和 prADMA 在各组之间没有差异，但存在相关性（r=0.728，P=0.0003，n=20）。acT1D 大鼠的脾脏和肾脏中 prCit 水平低于 ngCo 大鼠。cuT1D 大鼠的脾脏中 prADMA 水平高于 chT1D 大鼠，但胰腺中 prADMA 水平没有差异。联合治疗恢复了正常血糖，并增加了脾脏中的 prADMA，而不改变胰腺中的 prADMA 和 prCit。Western blot 显示存在不同的 prADMA 模式，特别是脾脏和胰腺中存在约 50-kDa 的 prADMA，而胰腺中仅存在约 25-kDa 的 prADMA，肾脏中仅存在非常微弱和小的 prADMA。除了在不同代谢状态下胰腺的变化外，脾脏在识别 T1D 的代谢变化方面可能比迄今为止认为的发挥更强的作用。
