Atorvastatin improves β-cell dysfunction by regulating pancreatic apoptosis in KKAy mice with impaired glucose tolerance

Objective To evaluate the effects of the atorvastatin( Ator)on β cell function in KKAy mice with impaired glucose tolerance( IGT-KKAy). Methods Female KKAy mice selected by insulin tolerance test( ITT) were divided into two groups. Model group was orally administered by gavage with water,Ator group at a dose of 30 mg·kg- 1·d- 1for about 46 days. Normal C57 mice were recruited as Nor group. ITT,glucose tolerance tests( OGTT) and fasting plasma lipids and insulin levels were determined. Pancreas weight index was tested. Pancreas morphology changes and β cell mass were evaluated by hematoxylin- eosin and gomori- aldehyde fuchsin stainning. The changes of gene and protein expression in the pancreas were also analyzed by Real- time- PCR and Western bolt. Results Ator significantly improved glucose intolerance and insulin resistance in IGT- KKAy mice. Lipid profiles such as triglyceride( TG),total cholesterol( CHO),free fatty acid( FFA) and low density lipoprotein cholesterol( LDL- C) were all significantly diminished after Ator treatment. Fasting plasma insulin levels and homeostatic model assessment- insulin resistance( HOMA- IR) index were also decreased after treatment. In addition,Ator markedly increased pancreas weight index,improved islets periphery and recovered β cell mass.It was showed that Ator up- regulated the pancreatic gene expression of anti- apoptotic Bcl-2 and cholesterol metabolism related SREBP2( P 0. 01,P 0. 05). Moreover,the protein expression of ER stress related Chop is decreased in Ator group( P0.01). Conclusion These results indicated that chronic administration of Ator improved dyslipidemia and glucose homeostasis in IGT- KKAy mice,which is related to up- regulation of genes involved in lipid metabolism and anti- apoptosis.The findings of the present study indicate that Ator might have a potential role for protecting β cell function.