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

Abstract

The present study investigates the effect s of troxerutin ( TX ) on insulin signaling in the heart of high fat, high fructose diet (HFFD) - induced insulin resistant mice . Adult male Mus m usculus mice of body weight 25 – 30 g were used for the study . HFFD was fed to animals to induce insulin resistance . O n the 16 th 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 contr ol diet and TX unsupplemente d HFFD - fed mice were also maintain ed . 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 - β (IR - β) an d insulin receptor substrate - 1 (IRS - 1). The assoc iation 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, hyperinsu linemia and enhanced tyrosine phosphorylation of IR - β, 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 promote s insulin action in the heart. Thus, TX c ould be a promising a ge n t for the management of insulin resistance.