Lp-Pla2 selective inhibitor (Darapladib) effect in lowering insulin resistance and aortic tissue inflammation at type 2 diabetes mellitus

Lipoprotein-associated phospholipase A2 (Lp-PLA₂) is an enzyme with several pro-inflammatory properties that involved in the pathogenesis of atherosclerosis but some investigation shows controversial views regarding its biological role. We examined the effect of a selective inhibitor of Lp-PLA₂ (darapladib) to the inflammation marker such as nuclear factor kappa B (NF-κB) and interleukin-6 (IL-6) expression in aortic tissue and insulin resistance of type 2 diabetes mellitus (T2DM) rat model. 30 Sprague-dawley rats were randomly divided into the normal group, T2DM group and T2DM with darapladib treatment. Induction of T2DM was done by giving high-fat diet and low dose injection of streptozotocin. Blood glucose level and insulin plasma concentration were measured to calculate insulin resistance in mice. Eight weeks and sixteen weeks after treatment, we compared expression of NF-κB and IL-6 in aortic tissue. Darapladib treatment group exhibited significant reduction of insulin resistance (0.64+0.11 vs 2.07+0.16, p < 0.05 at 8 weeks; and 0.93+0.08 vs 6.48+0.55 at 16 weeks) compared with T2DM group. On immunofluorescence analysis, darapladib significantly decreased NF-κB and IL-6 expression at 2 serial treatments. These data suggested that Lp-PLA₂ played a role in inflammation process and improve insulin resistance occurring in the metabolic disorder.