title: Oligomers of grape-seed procyanidin extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin.
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.
authors.affiliation: Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona 43007, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Montagut
authors.forename: Sheela
authors.initials: S
authors.lastname: Onnockx
authors.forename: Montserrat
authors.initials: M
authors.lastname: Vaqué
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Larrea
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
authors.forename: M Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pirson
authors.forename: Anna
authors.initials: A
authors.lastname: Ardévol
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D016466:CHO Cells; D002392:Catechin / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects*; D012639:Seeds / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D027843:Vitis / Q000378:metabolism*
chemical_list: D044946:Biflavonoids; D007328:Insulin; D010936:Plant Extracts; D044945:Proanthocyanidins; C017674:procyanidin; D002392:Catechin; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose