Attenuation of glucose transport across Caco‐2 cell monolayers by a polyphenol‐rich herbal extract: Interactions with SGLT1 and GLUT2 transporters

Abstract

Previous studies have indicated that secondary plant metabolites may modulate glucose absorption in the small intestine. We have characterized a polyphenol-rich herbal extract and its potential intestinal metabolites by LC-MS(2) and investigated the inhibition of glucose transporters SGLT1 and GLUT2 using the well-characterized Caco-2 intestinal model. Differentiated Caco-2 monolayers were incubated with an extract of a mixture of herbs and spices. Glucose transport under sodium-dependent and sodium-free conditions was determined by radiochemical detection of D-[U-(14) C]-glucose. A 54% decrease in transport was observed compared to control. Using sodium-dependent and sodium-free conditions, we demonstrate that the inhibition of GLUT2 was greater than SGLT1. Glycosidase and esterase enzymatic hydrolysis was used to assess the impact of metabolism on the efficacy of inhibition. Glucose transport across the membrane was reduced by 70% compared to the control and was associated with significant increases in flavonoid aglycones, caffeic acid, and p-coumaric acid. These results suggest that intact and hydrolyzed polyphenols, likely to be found in the lumen after ingestion of the supplement, play an important role in the attenuation of glucose absorption and may have potentially beneficial antiglycemic effects in the body.

Acute selective bioactivity of grape seed proanthocyanidins on enteroendocrine secretions in the gastrointestinal tract

“…Our results suggest an inhibition of intestinal gluconeogenesis by acute GSPE treatment. The increased portal glucose may therefore be due to reduced glucose uptake by the liver and pancreas, since polyphenols have been previously shown to inhibit the glucose transporter Glut-2 [21,22] and GSPE down-regulates the glucose transporter Glut-2 and glucokinase expression in liver and pancreas [23]. Certainly, considering that glucose may control hunger sensation from the portal vein via signalling to the peripheral neural system [24], increasing portal glucose levels during fasting could, at least in part, contribute to the previously reported [5] satiating effects of GSPE.…”

The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

“…The role of polyphenols in the regulation of the apical transporters has been widely studied (121–127). Several compounds have been shown to interfere with these transporters such as berry anthocyanins, apple polyphenols (phlorizin, quercetin, kaempferol, phloretin, and chlorogenic acid), helichrysum, and grapefruit (kaempferol-3-O-glucoside, chlorogenic acid-3-O-glucoside, naringenin-7-O-glucoside, naringenin diglycoside, kaempferol rutinoside, naringenin-7-O-rutinoside, and quercetin monoglucosides, among others) (121–126).…”

“…Several compounds have been shown to interfere with these transporters such as berry anthocyanins, apple polyphenols (phlorizin, quercetin, kaempferol, phloretin, and chlorogenic acid), helichrysum, and grapefruit (kaempferol-3-O-glucoside, chlorogenic acid-3-O-glucoside, naringenin-7-O-glucoside, naringenin diglycoside, kaempferol rutinoside, naringenin-7-O-rutinoside, and quercetin monoglucosides, among others) (121–126). Although the effect of PACs on these transporters was not evaluated so far, it is possible that they may exert certain activity, since flavanol monomers such as catechin, epicatechin, epigallocatechin, epicatechingallate, and epigallocatechingallate have been shown to inhibit SGLT1 or GLUT2 (128, 129).…”

The Effect of Isomaltulose Together with Green Tea on Glycemic Response and Antioxidant Capacity: A Single-Blind, Crossover Study in Healthy Subjects

“…Our findings are consistent with previous studies that the consumption of green tea together with sucrose reduces postprandial glucose and insulin concentration. The possible mechanisms of flavonoid-enriched green tea for reducing postprandial glucose include the inhibition of α-glucosidase activity, intestinal sodium-glucose co-transporter-1 (SGLT-1) and glucose transport-2 (GLUT-2) [35,36,37]. Furthermore, the flavins and catechins preferentially inhibited maltase rather than sucrose [38].…”