Adiponectin regulation of AMPK on oleanolic acid treated insulin resistance Sprague Dawley rats

Abstract

AMPK is the principal regulator of both glucose and lipid metabolic pathways, both critical in the etiology of type-2 diabetes (T2D). Various studies have dermnstrated that AMPK can be activated by the adiponectin Individuals suffering from T2D are known to have low adiponectin levels in their blood plasma. This study was aimed at assessing the effect of the anti-diabetic compound oleanolic acid (OA) on adiponectin levels and the subsequent regulation of AMPK. In addition, the study also assessed the influence of OA on the inflammatory cytokines, biormlecules that also play role in the development of T2D. In this study, Sprague Dawley rats were fed with a high fructose diet (HFD) to induce metabolic disturbance as a rmdel for T2D. The rats that developed metabolic disturbances were considered as diseased, and were consequentially treated with OA. Analysis of adiponectin concentration in blood plasma, AMPK gene expression and subsequent genes that play vital roles in glucose and lipid metabolism (GLUT-4 & CPT-1) were studied using rat skeletal muscle. Lastly, inflammatory cytokine gene expression (IL_6 & IL_10) and inflammatory cytokine concentration levels (1NF-a, IlL-6,IL-10, MCP-1 & VEGF) were also assessed. The results from these studies show a significant increase in blood plasma adiponectin concentration in OA treated rats compared to the untreated rats. Furthermore, OA significantly up-regulated AMPK gene expression with ~4-fold increase and GLUT-4 gene expression with ~1.5-fold. On the other hand, the CTP-1 gene expression was not significantly expressed. All inflammatory cytokines were significantly down-regulated by treatment with OA. However, when a HFD (high fructose diet) was fed to these rats, these cytokines were up-regulated. These results clearly indicate that OA produced desired effects in ameliorating insulin resistance or metabolic disturbance. In conclusion, this study further confirms that OA can be used as an effective therapeutic agent to ameliorate the symptoms of T2D. Furthermore, this study also suggest that OA's mechanism of action could be through AMPK pathway.