ginsenoside-rh4 and Diabetes-Mellitus--Type-2

The aim of this study is to investigate the hypoglycemic mechanism of ginsenoside Rh4 (G-Rh4) in vivo and in vitro models. Our results showed that G-Rh4 markedly improved the symptoms of diabetes, normalized glucose metabolism, and promoted insulin secretion which contributed to attenuate symptoms of hyperglycemia in high-fat diet/streptozocin induced type 2 diabetes mellitus mice. This positive effect was associated with increased expression of Nrf2 by G-Rh4. Further results demonstrated that G-Rh4 promoted Nrf2 nucleus translocation as well as up-regulated the expression of HO-1, NQO1 and GCLC. Furthermore, we also found that G-Rh4 increased insulin secretion by activating the signal pathway of PDX-1, GLUT2 and GCK. More importantly, the protective effects of G-Rh4 on alloxan-induced upregulation of Nrf2 target gene and insulin secretion were abolished by Nrf2 knockdown. Finally, we explored the mechanism of G-Rh4 associated with Nrf2 activation and found that the Akt deficiency inhibited G-Rh4-mediated Nrf2 nuclear translocation. Altogether, we present evidence that G-Rh4 increased expression of Nrf2 and results in increased antioxidant gene, as well as a rise in insulin secretion in vivo and in vitro. Exploiting the Nrf2 pathway may show great potential as a therapeutic strategy to improve pancreatic β-cells dysfunction in the diabetic population.

Topics: Alloxan; Animals; Cell Line; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Gene Knockdown Techniques; Ginsenosides; Glutamate-Cysteine Ligase; Heme Oxygenase-1; Insulin-Secreting Cells; Male; Membrane Proteins; Mice, Inbred C57BL; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Rats; RNA, Small Interfering; Signal Transduction; Up-Regulation