Liver paraoxonase 3 expression and the effect of liraglutide treatment in a rat model of diabetes.

BACKGROUND: This study investigated liver expression of paraoxonase 3 (PON3), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and nuclear factor (NF)-κB in a rat model of type-2 diabetes mellitus (T2DM), and assessed the effect of liraglutide treatment. OBJECTIVES: To investigate liver PON3 expression in rats withT2DM assess its role in disease pathogenesis, and determine the effect of liraglutide on its expression. MATERIAL AND METHODS: Type 2 diabetes mellitus was induced in 3 groups of rats: positive control group (PC; no treatment), and low-dose (LL; 100 μg/kg) and high-dose (HL; 200 μg/kg) liraglutide groups. Healthy rats served as a normal control (NC) group. Protein and mRNA expression were measured with western blot and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: After liraglutide treatment, fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), fasting insulin (FINS), malondialdehyde (MDA), and interleukin 6 (IL-6) levels were lower in HL rats compared with LL ones (p < 0.05). Compared to NC rats, FPG, FINS, HOMA-IR, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and IL-6 levels were the lowest in HL rats, followed by LL and PC ones (p < 0.05). Body weight (BW) was lower in LL and HL groups than in NC and PC (p < 0.05). The liver expression of PON3, PI3K and Akt were the highest in HL rats, followed by LL and PC (p < 0.05). The NF-κB expression was the lowest in HL rats, followed by LL and PC (p < 0.05). The PON3 expression was decreased in the diabetic rat liver. CONCLUSIONS: Liraglutide can increase PI3K, Akt and PON3 expression, and decrease NF-κB expression. The effect of liraglutide on improving insulin resistance and abnormal glucolipid metabolism in T2DM rats may be associated with increased liver PON3 expression.