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BACKGROUNDThis 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.OBJECTIVESTo investigate liver PON3 expression in rats withT2DM assess its role in disease pathogenesis, and determine the effect of liraglutide on its expression.MATERIAL AND METHODSType 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.RESULTSAfter 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.CONCLUSIONSLiraglutide 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.

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