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Updated: Jun 18, 2026

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Published on: May 10, 2018
Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance
Gemma Montagut1, Cinta Bladé, Mayte Blay
1Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona, 43007 Spain.
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.
Insights
Grape seed procyanidin extract (GSPE) shows promise for improving glucose homeostasis and insulin resistance. A daily dose of 25 mg/kg GSPE positively impacts metabolic health, particularly in adipose tissue.
Area of Science:
- Biochemistry
- Metabolic Syndrome Research
- Nutraceuticals
Background:
- Flavonoids, like those in grape seed procyanidin extract (GSPE), are recognized for potential benefits against metabolic syndrome risk factors.
- However, their precise mechanisms in modulating glucose homeostasis remain incompletely understood.
Purpose of the Study:
- To investigate the efficacy of GSPE in stimulating glucose uptake in insulin-resistant cells.
- To evaluate the effects of GSPE on glucose metabolism and insulin resistance in hyperinsulinemic animal models.
Main Methods:
- Assessed GSPE's glucose uptake stimulation in 3T3-L1 adipocytes resistant to insulin or dexamethasone.
- Administered varying doses of GSPE to hyperinsulinemic rats fed a cafeteria diet for 30 days.
- Analyzed plasma insulin, Homeostasis Model Assessment-insulin resistance (HOMA-IR) index, and gene expression (Pparg2, Glut4, Irs1) in adipose tissue.
Main Results:
- GSPE demonstrated higher glucose uptake stimulation than insulin in insulin-resistant adipocytes, but was less effective when resistance was induced by dexamethasone.
- GSPE treatment reduced plasma insulin levels and improved the HOMA-IR index in hyperinsulinemic rats.
- A daily dose of 25 mg/kg GSPE down-regulated key adipocyte markers (Pparg2, Glut4, Irs1) in mesenteric white adipose tissue, while preserving acute glucose uptake responsiveness.
Conclusions:
- A daily dose of 25 mg/kg GSPE exerts a positive long-term effect on glucose homeostasis, potentially by targeting adipose tissue for direct glucose uptake stimulation.
- The study underscores the importance of considering bioactive dosage, as higher concentrations do not invariably yield greater benefits.
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