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

Abstract

The endocrine pancreas plays a key role in metabolism. Procyanidins (GSPE) targets β-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.

Differential effects of a cafeteria diet and GSPE preventive treatments on the enterohormone secretions of aged vs. young female rats

“…2). This situation differs from the effects observed in young animals, 11 independently of the fed/fasted situation (unpublished results). GSPE PRE treatment showed different trends between aged and young animals.…”

“…These authors showed an attenuated anorectic effect of GLP-1 after this short cafeteria diet. 34 The GSPE treatment before the cafeteria diet was very effective in young rats, increasing ileum GLP-1 mRNA, together with GLP-1R, 10 as well as pancreas GLP-1R, 11 giving these animals a higher pancreatic sensitivity to GLP-1. However, we found a different situation in 21-month-old rats.…”

“…10 This GSPE treatment favours the endocrine pancreas having a higher sensitivity to incretins. 11 A GSPE dose with satiating effects clearly acts on the gastrointestinal wall where it modulates the secretion of the enterohormone, and thus has an impact on the food intake during the treatment. 12 Moreover, some effects also remained several months after the treatment.…”

Grape seed proanthocyanidin extract targets p66Shc to regulate mitochondrial biogenesis and dynamics in diabetic kidney disease

“…However, it is worth noting that GSPE also had hypoglycemic and weight-reducing effects in healthy rats. The mechanisms of GSPE affecting metabolism may be affecting the function of pancreatic β-cells, preventing the effect of a high-fat diet on pancreatic insulin secretion, Frontiers in Pharmacology frontiersin.org regulating intestinal microflora, and upregulating intestinal GLP-1 receptor expression (Liu et al, 2020;Grau-Bové et al, 2021). Accumulating evidence has demonstrated that hyperglycemia, high ROS production, and mitochondrial dysfunction are implicated in the development of DKD (Brownlee, 2005;Reidy et al, 2014;Jha et al, 2016).…”

GSPE Pre-Treatment Exerts Long-Lasting Preventive Effects against Aging-Induced Changes in the Colonic Enterohormone Profile of Female Rats

“…Atthe GIT, a dose of GSPE modulates enterohormone secretion, which has a satiating effect on food intake during treatment [24]. Treatment with GSPE improves the endocrine pancreas function and produces higher sensitivity to incretin hormones [25]. Moreover, some of these effects are maintained several months after the end of the treatment [26].…”