Evaluation of the Effect of Co-administration of IRAK Inhibitor and Pioglitazone on PPAR-γ, GLUT-۴, TNF-α, and Leptin Genes Expression in Adipose Tissue of Insulin-resistant Mice

Background: The worldwide prevalence of diabetes is increasing. Diabetes is a complex disease that results from impaired secretion of insulin or insulin resistance. In adipose tissue, insulin increases glucose uptake by stimulating the transfer of glucose transporter type ۴ (GLUT-۴) to the plasma membrane. In this study, the effect of IRAK inhibitor (IRAKi) and pioglitazone on genes expression in adipose tissue of insulin resistant mice was evaluated. Methods: Mice were randomly divided into ۶ groups (n= ۸ each), five groups of which were fed a high-fat diet and one group received a normal diet for ۱۲ weeks. The treatment with pioglitazone and IRAKi was performed for ۲ weeks. At the end of the study, the animals were sacrificed and the adipose tissue and blood samples were collected. The expression of GLUT۴, TNF-α, peroxisome proliferator-activated receptor gamma (PPARγ), and Lepin were determined by real-time PCR in the adipose tissue. The malondialdehyde (MDA) level and total antioxidant capacity (TAC) in serum were measured. Results were analyzed by SPSS ۲۲. Results: The data showed that the combination of IRAKi and pioglitazone increased PPARγ expression, leptin and TAC levels in serum, and reduced TNF-α expression and MDA levels. The GLUT۴ expression in adipose tissue was not significant between studied groups. Pioglitazone and IRAKi improved insulin function by inhibiting inflammation signaling. Conclusion: According to the results of this study, IRAKi may be an appropriate target for inhibiting inflammation and related disorders, including insulin resistance.

Keywords:

Diabetes Mellitus , insulin resistance , IRAK Inhibitor , GLU۴ , PPARγ , Pioglitazone