Estimation of Ellagic acid and/or Repaglinide Effects on Insulin Signaling, Oxidative Stress and Inflammatory Mediators of Liver, Pancreas, Adipose Tissue and Brain in Insulin Resistant/Type 2 Diabetic Rats

ABSTRACT

Even though ellagic acid was valued before in many models of cancer, so far its full mechanistic effect has not been deeply elucidated, which is the goal of this study. For that reason, we observed its 2 weeks influence of ellagic acid (10mg/kg, p.o b.wt.) and/or repaglinide (0.5mg/kg, p.o b.wt.) on insulin resistant/type 2 diabetic albino rats induced by high fat fructose diet (HFFD) diet for 2 months. On the serum biochemical level, ellagic acid challenged the HFFD consequence, where it showed a significant improvement in the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adepokines, ammonia and manganese. While in the tissue level (Liver, Pancreas, Adipose Tissue and Brain), it revealed a significant enhancement in insulin signaling, auto phosphorylation process, adiponectin receptors, glucose transporters, inflammatory mediators and apoptotic markers. Additionally, ellagic acid mitigated also the decreased locomotor activity. Amazingly, combined treatment of both ellagic acid and repaglinide displayed a more pronounced effect which overrides that of either treatment alone. These outcomes give a new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.