Grape Seed-Derived Procyanidins Have an Antihyperglycemic Effect in Streptozotocin-Induced Diabetic Rats and Insulinomimetic Activity in Insulin-Sensitive Cell Lines

Abstract

Flavonoids are functional constituents of many fruits and vegetables. Some flavonoids have antidiabetic properties because they improve altered glucose and oxidative metabolisms of diabetic states. Procyanidins are flavonoids with an oligomeric structure, and it has been shown that they can improve the pathological oxidative state of a diabetic situation. To evaluate their effects on glucose metabolism, we administered an extract of grape seed procyanidins (PE) orally to streptozotocin-induced diabetic rats. This had an antihyperglycemic effect, which was significantly increased if PE administration was accompanied by a low insulin dose. The antihyperglycemic effect of PE may be partially due to the insulinomimetic activity of procyanidins on insulin-sensitive cell lines. PE stimulated glucose uptake in L6E9 myotubes and 3T3-L1 adipocytes in a dose-dependent manner. Like insulin action, the effect of PE on glucose uptake was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase and to SB203580, an inhibitor of p38 MAPK. PE action also stimulated glucose transporter-4 translocation to the plasma membrane. In summary, procyanidins have insulin-like effects in insulin-sensitive cells that could help to explain their antihyperglycemic effect in vivo. These effects must be added to their antioxidant activity to explain why they can improve diabetic situations.

Effects of Grape Seed Proanthocyanidin Extracts on Aortic Pulse Wave Velocity in Streptozocin Induced Diabetic Rats

“…Figure 1B shows the results of comparisons of FBG findings among groups C1, C2, DM, and DMT. The FBG of the diabetic rats was significantly higher than that of the control rats at 0, 4,8,12,16,20, and 24 weeks (P < 0:01), but GSPEs did not decrease FBG at 0, 4,8,12,16,20, and 24 weeks (P > 0:05). The results for body weights and FBG by three-way ANOVA are summarized in Table 1.…”

“…The other 50 rats received a single dose of STZ (55 mg/kg, injected into the tail veins) freshly dissolved in 0.1 mol/l sodium citrate buffer (pH 4.5) after a 12 h of overnight fasting. [20][21][22] Only rats with blood glucose higher than 16.7 mmol/l after 5 d were considered diabetic in the fasting state, by using an One Touch II Glucose Analyzer (Johnson and Johnson, Langhorne, PA). Ten rats with blood glucose levels of less than 16.7 mmol/l were excluded from the study.…”

Differential effects of grape-seed derived procyanidins on adipocyte differentiation markers in different in vivo situations

“…Some of the animals were treated with streptozotocin to obtain animals with Type 1 diabetes mellitus [3]. On the day of the experiment, the rats were fed an oral gavage of GSPE in aqueous solution (250 mg/kg body wt).…”

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

“…2 Among other properties, flavonoids are antigenotoxic, 3 antiatherogenic 1,4 and ameliorators of diabetes. 5 Their effects on proliferation and differentiation have been studied both in cancerous and noncancerous cell lines. 1,6,7 However, there is little information about their effects on adipocytes.…”