Protective Effect Of Silibinin On Islet Beta Cells Against Glucolipotoxicity In Mice

Objective:To investigate the protective effect of silibinin on beta cells against glucolipotoxicity in C57BL/6J mice fed a high-fat diet and the possible mechanisms.Method:eighteen male C57BL/6J mice,3-week-old,were randomly divided into normal chow(NC) group, which were fed on normal diet, high-fat diet(HF)group, which were fed on high-fat diet(normal diet adding30%lard and1%cholesterol), and high-fat diet plus silibinin (HFS)group, which were also fed on high-fat diet. HFS group were given silibinin200mg· kg-1·d-1, the other two groups were given normal sodium chloride every day. After intervention for10weeks, fasting blood glucose, fasting insulin, triglycerides, alanine aminotransferase, creatinine and blood urea nitrogen were determined, and pancreatic fragment were used for evaluating lipid metabolism, antioxidant enzyme activities and apoptosis. Pancreatic islets were isolated to assess Insig-1, SREBP-1c and FAS mRNA expression, also insig-1and SREBP-lc protein expression.Results:Compared to NC group, the weight and the level of blood glucose were increased in the HF group (P<0.05), and the level of plasma insulin was decreased in HF group (P<0.05). The levels of lipid content and oxidative stress in pancreas and the rates of beta cell apoptosis were higher in HF group than in NC group (P<0.05).The function of insulin secretion was improved and the level of glucose was decreased in HFS group compared with HF group (P<0.05). The levels of lipid content and oxidative stress in pancreas and the rates of beta cell apoptosis were lower in HFS group than in HF group (P<0.05),however no significant difference of body weight was found between HF and HFS group. Simultaneously, silybin promoted the expression of Insig-1in islets, while the expression of SREBP-1c and FAS was restrained (P<0.05). Moreover, our study showed no statistically significant difference in the levels of serum alanine aminotransferase, creatinine and blood urea nitrogen among three groups (P>0.05)Conclusion:Silibinin could protect islets in mice fed a high-fat diet, and this effect might be partly related to promotion of Insig-1signal pathway against glucolipotoxicity and antioxidation ability. Our study also demonstrated that silibinin administration for long-term presented a favorable safety.