EFFECT OF TROXERUTIN ON CARDIAC INSULIN SIGNALING IN HIGH FAT, HIGH FRUCTOSE DIET - INDUCED INSULIN RESISTANT MICE

Abstract

The present study investigates the effects of troxerutin (TX) on insulin signaling in the heart of high fat, high fructose diet (HFFD)-induced insulin resistant mice. Adult male Mus musculus mice of body weight 25–30 g were used for the study. HFFD was fed to animals to induce insulin resistance. On the 16 day a group of HFFD-fed mice were supplemented with TX (150 mg/Kg bw, p.o) till the end of the experimental period. Control mice fed control diet and TX- unsupplemented HFFD-fed mice were also maintained. Analyses were performed after 60 days in plasma and heart tissue of mice. HFFD-fed mice displayed higher levels of glucose and insulin, decreased tyrosine phosphorylation of insulin receptor- $\beta $ (IR- $\beta $) and insulin receptor substrate-1 (IRS-1). The association of p85 subunit of phosphotidyl inositol 3 kinase (PI3K) with IRS-1, subsequent Akt phosphorylation and GLUT-4 translocation were reduced. TX treatment to HFFD-fed mice reduced hyperglycemia, hyperinsulinemia and enhanced tyrosine phosphorylation of IR- $\beta $, IRS-1, IRS-1-PI3K association, Akt and GLUT-4 activation. These findings suggest that TX activates IRS–PI3K–Akt pathway of insulin signaling and thereby promotes insulin action in the heart. Thus, TX could be a promising agent for the management of insulin resistance.