Oligomers of grape-seed procyanidin extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin

Gemma Montagut, Sheila Onnockx, Monserrat Vaqué, Cinta Bladé, Mayte Blay, Juan Fernández-Larrea, Gerard Pujadas, M. Josepa Salvadó, Lluis Arola, Isabelle Pirson, Anna Ardévol, Monserrat Pinent

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    Abstract

    Procyanidins are bioactive flavonoid compounds from fruits and vegetables that possess insulinomimetic properties, decreasing hyperglycaemia in streptozotocin-diabetic rats and stimulating glucose uptake in insulin-sensitive cell lines. Here we show that the oligomeric structures of a grape-seed procyanidin extract (GSPE) interact and induce the autophosphorylation of the insulin receptor in order to stimulate the uptake of glucose. However, their activation differs from insulin activation and results in differences in the downstream signaling. Oligomers of GSPE phosphorylate protein kinase B at Thr308 lower than insulin does, according to the lower insulin receptor activation by procyanidins. On the other hand, they phosphorylate Akt at Ser473 to the same extent as insulin. Moreover, we found that procyanidins phosphorylate p44/p42 and p38 MAPKs much more than insulin does. These results provide further insight into the molecular signaling mechanisms used by procyanidins, pointing to Akt and MAPK proteins as key points for GSPE-activated signaling pathways. Moreover, the differences between GSPE and insulin might help us to understand the wide range of biological effects that procyanidins have.
    Original languageEnglish
    Pages (from-to)476-481
    Number of pages6
    JournalJournal of Nutritional Biochemistry
    Volume21
    Issue number6
    DOIs
    Publication statusPublished - Jun 2010

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  • Cite this

    Montagut, G., Onnockx, S., Vaqué, M., Bladé, C., Blay, M., Fernández-Larrea, J., Pujadas, G., Salvadó, M. J., Arola, L., Pirson, I., Ardévol, A., & Pinent, M. (2010). Oligomers of grape-seed procyanidin extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin. Journal of Nutritional Biochemistry, 21(6), 476-481. https://doi.org/10.1016/j.jnutbio.2009.02.003