title: Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance.
abstract: Flavonoids are beneficial compounds against risk factors for metabolic syndrome, but their effects and the mechanisms on glucose homeostasis modulation are not well defined. In the present study, we first checked the efficacy of grapeseed procyanidin extract (GSPE) for stimulating glucose uptake in insulin-resistant 3T3-L1 adipocytes. Results show that when resistance is induced with chronic insulin treatment, GSPE maintain a higher stimulating capacity than insulin. In contrast, when dexamethasone is used as the resistance-inducing agent, GSPE is less effective. Next we evaluated how effective different GSPE treatments are at improving glucose metabolism in hyperinsulinemic animals (fed a cafeteria diet). GSPE reduced plasma insulin levels. The lower dose (25 mg GSPE/kg body weight per day) administered for 30 days improved the HOmeostasis Model Assessment-insulin resistance index. This was accompanied by down-regulation of Pparg2, Glut4 and Irs1 in mesenteric white adipose tissue. Similarly, a chronic GSPE treatment of insulin-resistant 3T3-L1 adipocytes down-regulated the mRNA levels of those adipocyte markers, although cells were still able to respond to the acute stimulation of glucose uptake. In summary, 25 mg/kg body weight per day of GSPE has a positive long-term effect on glucose homeostasis, and GSPE could be targeted at adipose tissue, where it might directly stimulate glucose uptake. This work also highlights the need to carefully consider the bioactive dose, since a higher dose does not necessarily correlate to a greater positive effect.
authors: Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona, 43007 Spain.
authors: Gemma
authors: G
authors: Montagut
authors: Cinta
authors: C
authors: Bladé
authors: Mayte
authors: M
authors: Blay
authors: Juan
authors: J
authors: Fernández-Larrea
authors: Gerard
authors: G
authors: Pujadas
authors: M Josepa
authors: MJ
authors: Salvadó
authors: Lluís
authors: L
authors: Arola
authors: Montserrat
authors: M
authors: Pinent
authors: Anna
authors: A
authors: Ardévol
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D044946:Biflavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002392:Catechin / Q000302:isolation & purification / Q000494:pharmacology*; D017931:DNA Primers; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds / Q000737:chemistry*; D027843:Vitis / Q000196:embryology*
chemical_list: D044946:Biflavonoids; D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D044945:Proanthocyanidins; C017674:procyanidin; D002392:Catechin