Glucose consumption and uptake in HepG2 cells is improved by aqueous extracts from leaves, but not rhizomes, of Posidonia oceanica (L.) Delile via GLUT-4 upregulation

The endemic Mediterranean seagrass Posidonia oceanica is a valuable source of natural bioactive compounds that possess significant therapeutic potential. Here, we examined whether aqueous extracts of rhizomes (RE) and green leaves (GLE) of P. oceanica could exert a glucose-lowering effect on the HepG2 cell line, chosen as an in vitro model of liver cells. We assessed glucose uptake and storage, expression levels of GLUT-2 and -4 transporters and the exposure of the latter one at cell surface, as well as modulation of the expression, synthesis and/or activation of the GLUT2-transcription factor hepatocyte nuclear factor-1 alpha (HNF1α), and insulin receptor substrate-1 (IRS-1), AKT and protein kinase Cζ (PKCζ), which regulate GLUT-4 translocation. Glucose consumption/uptake and glycogen storage were increased with exposure to GLE alone. Furthermore, at the molecular level GLE-induced upregulation of (i) IRS-1, AKT, and PKCζ activation levels, (ii) GLUT-4 translation levels, and (iii) GLUT-4 exposure on the cell surface. Conversely, GLUT-2 protein was downregulated. Therefore, the application of the aqueous extract of green leaves of P. oceanica may be suitable for the development of new treatment agents or dietary supplements for diabetes mellitus acting through GLUT-4 mediated glucose import.