Inhibition of the facilitative sugar transporters (GLUTs) by tea extracts and catechins

Ni, Dejiang; Ai, Zeyi; Munoz-Sandoval, Diana; Suresh, R.; Ellis, Peter R.; Chen, Yuqiong; Sharp, Paul; Butterworth, Peter J.; Yu, Zhi; Corpe, Christopher

doi:10.1096/fj.202000057rr

Cited by 30 publications

(22 citation statements)

References 61 publications

(138 reference statements)

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“…It has been suggested that EGCG (and quercetin) may exert much slower but more effective inhibition of disaccharide digestion in the intestine [75]. EGCG potently reduced glycaemic response in a diabetic animal model by binding to the active site of α-amylase and α-glucosidase [76] and decreased glucose uptake and GLUT2 expression in vitro [77]. However, a recent systematic review and meta-analysis from fourteen eligible articles demonstrated that the regular intake of EGCG-rich green tea had no significant effects on fasting blood glucose and insulin, HbA1c or HOMA-IR in T2D patients [78], which may be partially explained by the weak inhibition towards all three intestinal α-glucosidases shown in this study.…”

Section: Quercetinmentioning

confidence: 99%

Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Barber

Houghton

Williamson

2021

Foods

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Certain flavonoids can influence glucose metabolism by inhibiting enzymes involved in carbohydrate digestion and suppressing intestinal glucose absorption. In this study, four structurally-related flavonols (quercetin, kaempferol, quercetagetin and galangin) were evaluated individually for their ability to inhibit human α-glucosidases (sucrase, maltase and isomaltase), and were compared with the antidiabetic drug acarbose and the flavan-3-ol(−)-epigallocatechin-3-gallate (EGCG). Cell-free extracts from human intestinal Caco-2/TC7 cells were used as the enzyme source and products were quantified chromatographically with high accuracy, precision and sensitivity. Acarbose inhibited sucrase, maltase and isomaltase with IC50 values of 1.65, 13.9 and 39.1 µM, respectively. A similar inhibition pattern, but with comparatively higher values, was observed with EGCG. Of the flavonols, quercetagetin was the strongest inhibitor of α-glucosidases, with inhibition constants approaching those of acarbose, followed by galangin and kaempferol, while the weakest were quercetin and EGCG. The varied inhibitory effects of flavonols against human α-glucosidases depend on their structures, the enzyme source and substrates employed. The flavonols were more effective than EGCG, but less so than acarbose, and so may be useful in regulating sugar digestion and postprandial glycaemia without the side effects associated with acarbose treatment.

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Section: Quercetinmentioning

confidence: 99%

Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Barber

Houghton

Williamson

2021

Foods

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“…In vivo studies on animals have identified beneficial effects of EGCG including decreased adipose mass [ 35 ], reduction in body weight [ 36 ], and improvement in glucose homeostasis [ 35 , 36 , 37 ]. The effects of EGCG on glucose metabolism associated with T2D have been reported to be mediated in several ways including decreased gluconeogenesis [ 38 ], increased insulin sensitivity [ 39 ], and increased glucose uptake in skeletal muscle [ 40 ], which is an important regulator of glucose homeostasis [ 41 ]. The direct molecular targets of EGCG in vivo are not known.…”

Section: Resultsmentioning

confidence: 99%

Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme

et al. 2021

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The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 that has been linked to the neurodegeneration in Alzheimer’s disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE’s activity for the clearance of Aβ42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE’s activity toward Aβ42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE’s activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity.

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“…Caco-2 cells were seeded at a density of 8 × 10 4 cells per well in 6-well plates (Ni et al, 2020 ). After differentiation over a period of 21 days, cells were incubated with 2.0 mL of 200 μM theaflavins at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer

Liu

et al. 2021

Drug Delivery

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This study aimed to clarify the bioavailability mechanism of theaflavins by using the Caco-2 monolayer in vitro model. Prior to the transport of theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3’-gallate (TF3’G), and theaflavin-3, 3’-digallate (TFDG), we found the cytotoxicity of theaflavins was in the order of TF3’G > TFDG > TF3G > TF, suggesting the galloyl moiety enhances the cytotoxicity of theaflavins. Meantime, the galloyl moiety made theaflavins unstable, with the stability in the order of TF > TFDG > TF3G/TF3’G. Four theaflavins showed poor bioavailability with the P app values ranging from 0.44 × 10 −7 to 3.64 × 10 −7 cm/s in the absorptive transport. All the theaflavins showed an efflux ratio of over 1.24. And it is further confirmed that P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs) and breast cancer resistance protein (BCRP) were all shown to contribute to the efflux transport of four theaflavins, with P-gp playing the most important role, followed by MRPs and BCRP. Moreover, theaflavins increased the expression of P-gp, MRP1, MPR3, and BCRP while decreased the expression of MRP2 at the transcription and translation levels. Additionally, the gallated theaflavins were degraded into simple theaflavins and gallic acids when transported through Caco-2 monolayers. Overall, the structural instability, efflux transporters, and cell metabolism were all responsible for the low bioavailability of four theaflavins in Caco-2 monolayers.

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Inhibition of the facilitative sugar transporters (GLUTs) by tea extracts and catechins

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 30 publications

References 61 publications

Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme

Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer

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