Glucagon Shows Higher Sensitivity than Insulin to Grapeseed Proanthocyanidin Extract (GSPE) Treatment in Cafeteria-Fed Rats.

The endocrine pancreas plays a key role in metabolism. Procyanidins (GSPE) targets ß-cells and glucagon-like peptide-1 (GLP-1)-producing cells; however, there is no information on the effects of GSPE on glucagon. We performed GSPE preventive treatments administered to Wistar rats before or at the same time as they were fed a cafeteria diet during 12 or 17 weeks. We then measured the pancreatic function and GLP-1 production. We found that glucagonemia remains modified by GSPE pre-treatment several weeks after the treatment has finished. The animals showed a higher GLP-1 response to glucose stimulation, together with a trend towards a higher GLP-1 receptor expression in the pancreas. When the GSPE treatment was administered every second week, the endocrine pancreas behaved differently. We show here that glucagon is a more sensitive parameter than insulin to GSPE treatments, with a secretion that is highly linked to GLP-1 ileal functionality and dependent on the type of treatment.

Grape Seed Proanthocyanidins Target the Enteroendocrine System in Cafeteria-Diet-Fed Rats.

SCOPE: The effects on the enteroendocrine system of three different grape seed proanthocyanidin extract (GSPE) treatments are analyzed in rats on a cafeteria diet for 17 weeks. METHODS AND RESULTS: GSPE is administered in a corrective manner (15 last days of the cafeteria diet) at two doses, 100 and 500 mg GSPE per kg bw. A third, longer treatment in which GSPE (500 mg kg-1 bw) is administered daily every other week during the 17 weeks of the cafeteria diet is also tested. Most GSPE treatments lead to ghrelin accumulation in the stomach, limited CCK secretion in the duodenum, and increased GLP-1 and PYY mRNA in colon. GSPE also increases cecal hypertrophy and reduces butyrate content. When the treatment is administered daily every other week during 17 weeks, there is also an increase in colon size. These effects are accompanied by a reduced food intake at the end of the experiment when GSPE is administered at 500 mg GSPE kg-1 during the last 15 days, but not on the other treatments, despite an observed reduction in body weight in the longer treatment. CONCLUSION: GSPE modulates the enteroendocrine system in models in which it also reduces food intake or body weight.

Effects of an Intermittent Grape-Seed Proanthocyanidin (GSPE) Treatment on a Cafeteria Diet Obesogenic Challenge in Rats.

Obesity is highly associated with the pathologies included in the concept of the Metabolic Syndrome. Grape-seed proanthocyanins (GSPE) have showed very positive effects against all these metabolic disruptions; however, there is, as yet, no consensus about their effectiveness against an obesogenic challenge, such as a cafeteria diet. We determined the effectiveness of a dose of 500 mg GSPE/kg b.w. (body weight) against the obesogenic effects of a 17-week cafeteria diet, administered as a sub-chronic treatment, 10-15 days before, intermittently and at the end of the diet, in Wistar rats. Body weight, adiposity, indirect calorimetry and plasma parameters were analyzed. GSPE pre-treatment showed a long-lasting effect on body weight and adiposity that was maintained for seven weeks after the last dose. A corrective treatment was administered for the last two weeks of the cafeteria diet intervention; however, it did not effectively correct any of the parameters assessed. The most effective treatment was an intermittent GSPE dosage, administered every second week during the cafeteria diet. This limited body weight gain, adiposity and most lipotoxic effects. Our results support the administration of this GSPE dose, keeping an intermittent interval between dosages longer than every second week, to improve obesogenic disruptions produced by a cafeteria diet.