Department of Chemistry, Federal University of Mato Grosso, Av. Fernando Correa da Costa s/n, Coxipó, 78060-900 Cuiabá, Mato Grosso, Brazil.
J Ethnopharmacol. 2010 Aug 19;131(1):135-9. doi: 10.1016/j.jep.2010.06.015. Epub 2010 Jun 18.
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-hyperglycemic 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 associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction.
本实验室之前的研究表明，用大花紫玉盘茎皮的乙醇提取物（VmE）治疗 21 天的糖尿病大鼠，可降低血糖、尿糖和尿素，增加肝糖原含量，并改善其他与糖尿病相关的参数。本研究的目的是评估 VmE 的抗高血糖机制是否可以通过改善外周组织（肝脏、脂肪组织和骨骼肌）中的胰岛素信号通路来实现。
链脲佐菌素诱导的糖尿病大鼠分为两组：糖尿病对照组（DC）和糖尿病用 VmE 治疗组（DT），共治疗 21 天。通过 Western blot 分析测定胰岛素受体（IR）、蛋白激酶 B/AKT 含量和 AKT 磷酸化水平，研究了肝脏、腹膜后脂肪组织（RET）和伸趾长肌（EDL）中胰岛素信号的变化。同样的方法用于评估这些动物肝脏中的磷酸烯醇丙酮酸羧激酶（PEPCK）水平。
提取物的治疗增加了三种组织中 IR 的含量和 AKT 的基础磷酸化。在糖尿病治疗组的肝脏中，胰岛素刺激的 AKT 磷酸化更高，PEPCK 蛋白水平降低。
本工作的数据表明，大花紫玉盘茎皮提取物的抗高血糖活性可能通过刺激糖尿病大鼠外周组织中的胰岛素信号通路来实现，主要在肝脏和脂肪组织中，可能促进葡萄糖摄取和肝糖原合成增加。肝内 PEPCK 水平的同时降低可能与抑制糖异生有关，这也有助于降低血糖。
