Dangnyohwan improves glucose utilization and reduces insulin resistance by increasing the adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima Fatty rats

Abstract

Aim of the Study: Dangnyohwan (DNH) has been used for treatment of diabetes mellitus. However, the exact cellular and molecular mechanisms underlying the beneficial effects of DNH are not well understood. Therefore, we investigated how DNH improves hyperglycemia and insulin resistance in obese-type diabetes model. Methods and Materials: We examined the effect of DNH on the expression of glucose transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in muscle and adipose tissues from Otsuka Long-Evans Tokushima Fatty (OLETF) and Long–Evans Tokushima Otsuka (LETO) rats. Results: DNH ameliorated hyperglycemia and impaired glucose tolerance (IGT) observed in 26- and 42-week-old male OLETF rats. The basal and insulin-stimulated [ 14C]2-Deoxyglucose (2DG) uptake was significantly increased in adipocytes from DNH-treated OLETF rats, as compared with untreated OLETF rats. The expression level of GLUT4 was markedly decreased (by 90–95%) in the adipose tissue of OLETF rats, whereas DNH treatment drastically increased the expression of GLUT4 within 8 weeks. DNH improved GLUT4 recruitment stimulated by insulin in both the 26- and 42-week-old OLETF rat adipocytes. Conclusion: These results suggest that DNH could exert the beneficial effects on hyperglycemia and insulin resistance by increasing the expression and insulin-stimulated translocation of GLUT4 in OLETF rat adipocytes.