Thujone improves glucose homeostasis in streptozotocin-induced diabetic rats through activation of Akt/GSK-3β signaling pathway -

H. Alkhateeb
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引用次数: 5

Abstract

Objective: Thujone, a main constituent of medicinal herbs, has been shown to have antidiabetic properties. Therefore the primary objective of this study was to investigate the mechanism(s) by which thujone ameliorates diabetes and insulin resistance in streptozotocin (STZ)-induced diabetic rats. Methods: Male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (55 mg/kg). Thereafter, rats were randomly divided into three groups: normal control rats; STZ diabetic rats; STZ diabetic rats that received thujone by daily oral administration (60 mg/kg body weight) for 4 weeks. At the end of the experiment, blood sample was collected for determination of plasma glucose and insulin levels. Then, rats were sacrificed and liver was removed for further analysis, i.e. liver glycogen, Akt, glycogen synthase kinase (GSK)-3β and glycogen synthase (GS). Results: The results revealed that STZ administration resulted in significant elevation of the plasma glucose level and GS phosphorylation. In contrast, plasma insulin level and phosphorylation of both Akt and GSK-3β were inhibited as compared with control. Feeding the STZ-diabetic rats for 4 weeks with thujone normalized glucose level, but failed to normalize insulin level. These effects were accompanied with elevation in the phosphorylation of Akt and GSK-3 β. Moreover, the phosphorylation of GS was lower than the control group after thujone administration. Conclusion: These results clearly demonstrate that thujone exhibits a hypoglycemic effect in vivo that could be attributed, at least in part, to increasing hepatic glycogen synthesis via Akt/GSK-3β regulating pathway.
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图琼通过激活Akt/GSK-3β信号通路改善链脲佐菌素诱导的糖尿病大鼠葡萄糖稳态
目的:土琼酮是中药的主要成分之一,具有抗糖尿病作用。因此,本研究的主要目的是探讨图琼酮改善链脲佐菌素(STZ)诱导的糖尿病大鼠糖尿病和胰岛素抵抗的机制。方法:雄性Sprague-Dawley大鼠单次腹腔注射STZ (55 mg/kg)致糖尿病。随后,将大鼠随机分为三组:正常对照大鼠;STZ糖尿病大鼠;STZ糖尿病大鼠每日口服(60 mg/kg体重)4周。实验结束时,取血测定血糖和胰岛素水平。然后处死大鼠,取肝进一步分析肝糖原、Akt、糖原合成酶激酶(GSK)-3β和糖原合成酶(GS)。结果:STZ可显著提高大鼠血浆葡萄糖水平和GS磷酸化水平。与对照组相比,血浆胰岛素水平和Akt、GSK-3β磷酸化均受到抑制。给stz -糖尿病大鼠喂4周的图琼能使血糖水平正常,但不能使胰岛素水平正常。这些作用伴随着Akt和GSK-3 β磷酸化的升高。此外,给药后GS的磷酸化水平低于对照组。结论:这些结果清楚地表明,图琼酮具有体内降糖作用,这可能至少部分归因于通过Akt/GSK-3β调节途径增加肝糖原合成。
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