Involvement of the PI3K/AKT pathway in the hypoglycemic effects of saponins from Helicteres isora
2009
Bhavsar, Shefalee K. | Foller, Michael | Gu, Shuchen | Vir, Sanjay | Shah, Mamta B. | Bhutani, K.K. | Santani, Dev D. | Lang, Florian
Aim of the study: Saponins from Helicteres isora have previously been shown to exert antidiabetic effects. The present study explored the underlying mechanisms in C2C12 skeletal muscle cells. Materials and methods: C2C12 cells were incubated with saponins and sapogenin followed by Western blotting and immunofluorescence analysis. Results: Western blotting revealed that incubation with saponins (100μg/ml) and sapogenin (100μg/ml) induced the phosphorylation of the phosphatidylinositol-3-kinase (PI3K) as well as of the downstream targets protein kinase B/Akt (at Ser473) and glycogen synthase kinase GSK-3α/β (at Ser21/9) in a time-dependent manner. In contrast, no phosphorylation of the AMP-sensitive kinase AMPK (at Thr172) was observed. Within 48h saponins/sapogenin treatment further increased the protein abundance of the insulin-sensitive glucose transporter Glut4. Confocal microscopy confirmed that saponins/sapogenin treatment stimulated Akt phosphorylation and revealed that the treatment was followed by translocation of Glut4 into the cell membrane of C2C12 muscle cells. Conclusions: Saponins and sapogenin activate the PI3K/Akt pathway thus leading to phosphorylation and inactivation of GSK-3α/β with subsequent stimulation of glycogen synthesis as well as increase of Glut4-dependent glucose transport across the cell membrane.
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