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

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.