Effects of Flavanols on Enteroendocrine Secretion

Abstract

Some beneficial effects of grape seed proanthocyanidin extract (GSPE) can be explained by the modulation of enterohormone secretion. As GSPE comprises a combination of different molecules, the pure compounds that cause these effects need to be elucidated. The enterohormones and chemoreceptors present in the gastrointestinal tract differ between species, so if humans are to gain beneficial effects, species closer to humans-and humans themselves-must be used. We demonstrate that 100 mg/L of GSPE stimulates peptide YY (PYY) release, but not glucagon-like peptide 1 (GLP-1) release in the human colon. We used a pig ex vivo system that differentiates between apical and basolateral intestinal sides to analyse how apical stimulation with GSPE and its pure compounds affects the gastrointestinal tract. In pigs, apical GSPE treatment stimulates the basolateral release of PYY in the duodenum and colon and that of GLP-1 in the ascending, but not the descending colon. In the duodenum, luminal stimulation with procyanidin dimer B2 increased PYY secretion, but not CCK secretion, while catechin monomers (catechin/epicatechin) significantly increased CCK release, but not PYY release. The differential effects of GSPE and its pure compounds on enterohormone release at the same intestinal segment suggest that they act through chemosensors located apically and unevenly distributed along the gastrointestinal tract.

Keywords: CCK; GLP-1; PYY; flavonoids; intestine.

Figure 1

Enterohomone secretion levels in the basolateral medium after apical stimulation of pig intestinal segments with grape seed proanthocyanidin extract (GSPE). (a) Cholecystokinin (CCK) (orange columns) and peptide YY (PYY) (blue columns) secretion in duodenum. (b) Glucagon-like peptide 1 (GLP-1) secretion in ascending colon. (c) PYY (blue columns) and GLP-1 (green columns) secretion in descending colon. Results are expressed in arbitrary units (A.U.), which are values normalized versus the control and represent mean ± SEM. * p < 0.05 vs. control, # p < 0.1 t-test, n = 7–15.

Figure 2

Enterohormone levels in the basolateral side after apical stimulation of pig intestinal samples with different purified compounds, for 60 min. (a) PYY secretion in the duodenum, (b) CCK secretion in the duodenum, (c) GLP-1 secretion in the ascending colon. Results are expressed in arbitrary units (A.U.), which are values normalized versus the control and represent mean ± SEM. * p < 0.05 vs. control, # p < 0.1, t-test. n = 7–9. C-, negative control vehicle-treated; Cat, catechin; Epi, epicatechin; B2, B2 procyanidin dimer; GA, gallic acid; PCA, protocatechuic acid.

Figure 3

Enterohomone secretion in the medium after stimulation of human ascending (dark columns) and descending (light columns) colon explants with grape seed proanthocyanidin extract (GSPE, 100 mg/L). (a) PYY values, (b) total GLP-1 values. Results are expressed in arbitrary units (A.U.), which are values normalized versus the control and represent mean ± SEM. * p < 0.05 vs. control, t-test. n = 13–15 explants from 4–10 humans.

Figure 4

In pig duodenum, the different compounds of GSPE cause a selective enterohormone secretion. A possibility is that they act through different receptors that are related to a specific enterohormone secretion, either because they are expressed in cells containing only this hormone, or because they activate intracellular mechanisms that distinguish between hormones. Other compounds of the extract might antagonize the effects, or increase secretion through the same or other receptors. A similar pathway could take place in the colon, where differential GLP-1 and PYY secretion has been found.