Effects Of Probucol On PRMT1-ADMA-DDAH1 Axis In The Pancreas Of Type 2 Diabetic Rats

Objective: To establish the rat models of type 2 diabetes mellitus and to explore the expression of PRMT1 (protein-arginine methyl transferase1)–ADMA (asymmetric dimethy1arginine) -DDAH1 (dimethylarginine dimethylaminohydrolase1 ) axis in pancreas of diabetic rats, and the influence of Probucol on this axis and the function of pancreatic islets.Methods: Rats were assigned to control group (C, n=10), diabetes group (D, n=10) and Probucol group (P, n=10), respectively. The diabetic rat models were induced by injecting streptozotocin(STZ) and high fat and glucose breeding .After 8 weeks, the pancreatic tissues were collected for measuring .The content of ADMA in pancreas was evaluated in each group by ELISA, the expressions of PRMT1 and DDAH1 mRNA were determined and compared within each two groups by RT-PCR, the expression of PRMT1 protein in pancreas was determined in each group by WB, and the expressions of insulin and PRMT1 in pancreas were revealed in all the rats by IHC; meanwhile, the blood samples were collected to measure the level of FBG,FINS,MDA,SOD,CAT.Results: The content of ADMA in C, D and P was (464.50±53.83)μmol/L, (1255.34±188.00)μmol/L, (891.72±52.10)μmol/L. D and P significantly elevated compared to C (P<0.01), and D was significantly elevated compared to P (P<0.01); the expression of PRMT1 mRNA in D and P was significantly higher than C(P<0.01), and D was significantly higher than P (P<0.01), however, the expression of DDAH1 mRNA in D and P was significantly lower than C(P<0.01), and P was significantly higher than D (P<0.01); the results of WB and IHC revealed that the expression of PRMT1 in D and P was significantly higher than C(P<0.01), and D was significantly higher than P (P<0.01). The FBG levels of D and P group were significantly increased compared to C group (P<0.01), while no significant difference was observed between D and P group (P=0.624). Compared with C group, the FINS levels of D and P group were significantly decreased (P<0.01), but the FINS level of P group was significantly higher than D group (P<0.01). The levels of MDA in D and P group were increased than C group (P<0.01, P<0.05), while the level of MDA in P group was significantly lower than D group (P<0.01). The CAT and SOD levels of D and P group were significantly lower than C group (P<0.01), but the CAT and SOD levels of P group were significantly higher than D group (P<0.01).Conclusions: The expression of PRMT1-ADMA-DDAH1 axis in pancreas was impaired in diabetes condition. While the expression of PRMT1 was elevated, the expression of DDAH1 was reduced. Probucol regulated the expression of PRMT1-ADMA-DDAH1 axis in pancreas, reduced the oxidative stress and improved the function of pancreatic islets.