Evaluation of the effect of interleukin-1 receptor associated kinase (IRAK) inhibitor on PPAR.γ and GLUT.4 genes expression in muscle tissueof insulin resistant mice

Abstract

Background and Aim: Diabetes mellitus is a metabolic disorder with an increasing prevalence in the world. Obesity plays a pivotal role in increasing the risk of diabetes, metabolic syndrome, hypertension and cardiovascular diseases. Obesity dependent mild-inflammation leads to an imbalance in the secretion of adipokines and thereby reduces insulin sensitivity. The TLR family plays an important role in these inflammatory pathways, and therefore inhibition of IRAK, as a key mediator of the pathway, plays a role in inhibiting inflammation and insulin resistance. In this study we investigated the effect of this inhibitor on the expression levels of PPAR-γ and GLUT.4, which are involved in insulin sensitivity. Materials and Methods: In this study, male C57BL/6J mice were used for induction of insulin resistance. Mice were divided into 6 groups including standard diet, high fat diet, high fat diet + solvent, high fat diet + pioglitazone, high fat diet + IRAK inhibitor and high fat diet + combination of pioglitazone-IRAK inhibitor. At the end of the study, the mice were killed and expression levels of GLUT4 and TPPAR-γ in muscle tissue of the mice were measured by Real Time PCR. Results: This study showed that pioglitazone, IRAK inhibitor, and the combination of IRAK inhibitor- Pioglitazone increased PPAR-γ expression in muscle tissue, but IRAK inhibitor unlike pioglitazone had no effect on GLUT.4 expression. Conclusion: The results of this study suggested that insulin sensitizing effects of IRAK inhibitor may be induced by increasing PPAR-γ expression level.

Keywords

• diabetes mellitus
• insulin resistance
• irak inhibitor
• glut4
• ppar-γ
• pioglitazone