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.