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

Document Type : Original Article

Authors

1 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 Department of Biochemistry, Biophysics, Genetics and Nutrition, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran

3 Assistant Professor, Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

4 Assistant Professor, Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

10.22062/jkmu.2021.91608

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-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 22.
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 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.

Keywords


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