Evaluation of the effect of co-administration of irak inhibitor and pioglitazone on ppar-γ, glut-4, tnf-α, and leptin genes expression in adipose tissue of insulin-resistant mice

Abstract

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 4 (GLUT-4) 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 6 groups (n= 8 each), five groups of which were fed a high-fat diet and one group received a normal diet for 12 weeks. The treatment with pioglitazone and IRAKi was performed for 2 weeks. At the end of the study, the animals were sacrificed and the adipose tissue and blood samples were collected. The expression of GLUT4, TNF-I±, peroxisome proliferator-activated receptor gamma (PPARI³), 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 22. Results: The data showed that the combination of IRAKi and pioglitazone increased PPARI³ expression, leptin and TAC levels in serum, and reduced TNF-I± expression and MDA levels. The GLUT4 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. © 2021 The Author(s); Published by Kerman University of Medical Sciences.