Mechanism of anti-hyperglycemic action of Vatairea macrocarpa (Leguminosae): Investigation in peripheral tissues

The treatment of diabetic rats with stem-bark Vatairea macrocarpa ethanolic extract increased the insulin receptor content and the basal phosphorylation of AKT in liver, retroperitoneal adipose tissue and EDL muscles. The insulin-stimulated AKT phosphorylation was higher and the protein level of phosphoenolpyruvate carboxykinase (PEPCK) was reduced in the liver from diabetic-extract treated rats when compared with control rats. These data suggest that the anti-hyperglycemic activity of the V. macrocarpa extract may occur through stimulation of insulin signaling pathways mainly in liver and adipose tissue, and that an increase of glucose uptake and concomitant decrease of endogenous glucose production through neoglicogenesis could be contributing to the anti-hyperglycemic effects of the extract. Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglicemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle). Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals. The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be ass