The Emerging Role of Polyphenols in the Management of Type 2 Diabetes
Abstract
:1. Introduction
2. Regulation of GLP-1 Secretion
2.1. GLP-1 Physiology
2.2. Neuronal and Hormonal Regulation of GLP-1 Secretion
2.3. Nutritional Regulation of GLP-1 Secretion
3. Polyphenols
3.1. Polyphenols and GLP-1 Secretion
3.1.1. Polyphenols as Activators of GPCRs
3.1.2. Polyphenols as Regulators of cAMP Signaling
3.2. The Potential Role of Microbiota in Polyphenol-Stimulated GLP-1 Secretion
3.3. Polyphenols and DPP-IV
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AA | amino acid |
cAMP | cyclic adenosine monophosphate |
CaSR | calcium-sensing receptor |
CoA | coenzyme A |
CQA | caffeoylquinic acid |
D3R | delphinidin 3-rutinoside |
DAG | diacylglycerol |
DPP-IV | dipeptidyl-peptidase-IV |
EGCG | epigallocatechin gallate |
ERK1/2 | extracellular signal-related kinase 1/2 |
GIP | glucose-dependent insulinotropic peptide |
GLP-1 | glucagon-like peptide 1 |
GLP-1R | GLP-1 receptor |
GPCR | G-protein coupled receptor |
GP-AMC | Gly-Pro-7-amido-4-methylcoumarin hydrobromide |
GSGS | glucose stimulated GLP-1 secretion |
GSIS | glucose stimulated insulin secretion |
GSPE | Grape seed-derived proanthocyanidins |
FA | Fatty acid |
FFAR | FA receptor |
IP3 | inositol trisphosphate |
PDE | phosphodiesterase |
PEPT | peptide transporter |
PIP2 | Phosphatidylinositol 4,5-bisphosphate |
PLC | phospholipase C |
PK | protein kinase |
PUFA | Polyunsaturated fatty acid |
PYY | peptide tyrosine tyrosine |
SCFA | short-chain FA |
SGLT | sodium-dependent glucose transporter |
T2D | type 2 diabetes |
Tas1R | sweet taste receptor 1 |
Tas2R | sweet taste receptor 2 |
TRP | transient receptor potential |
TRPA1 | transient receptor potential ion channel A1 |
TRPM5 | transient receptor potential channel M5 |
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Polyphenolic Compounds | Chemical Structure | Dose | Model | Effect on GLP1 | Possible Mechanisms |
---|---|---|---|---|---|
Curcumin [125,127] | | 10 μM 1.5 mg/kg b.w. | Glutag L-cells, Rat | Increase GLP-1 secretion; increase plasma GLP-1 level | GPR40/120-dependent pathway |
Delphinidin 3-rutinoside [128] | | 10 μM | Glutag L-cells | Increase GLP-1 secretion | GPR40/120-dependent pathway |
EGCG [145,146,147] | | 300 μM 500 mg | Mouse ileum segment, diabetic patients | Increase GLP-1 secretion; increase plasma GLP-1 level | Tas2Rs-dependent pathway |
Genistein [165] | | 20 mg/kg b.w. | Alloxan-induced insulin deficient diabetic rats [165] | Increase tissue content of GLP-1 | cAMP signaling by activating AC |
Grifolic acid [132] | | 30 μM | STC-1 cells | Increase GLP-1 secretion | GPR120/Ca2+ signaling |
Grifolic acid methyl ether [132] | | 30 μM | STC-1 cells | Increase GLP-1 secretion | GPR120/Ca2+ signaling |
Hispidulin [166] | | 1 μM 20 mg/kg b.w. | Glutag L-cell, STZ-induced diabetic mice | Increase GLP-1 secretion; increase plasma GLP-1 level | Inhibiting PDE activity |
Silymarin [169] | | 100 mg/kg b.w. | Obese rats | Increased serum GLP-1 level | Inhibiting PDE activity |
Caffeoylquinic acid [173] | | IC50: 0.49 mM | Human plasma platelets | Not applicable | Inhibiting PDE activity |
Caffeic acid [173] | | IC50: 0.48 mM | Human plasma platelets | Not applicable | Inhibiting PDE activity |
Polyphenols | Polyphenolic Composition | Dose | Model | Effects on Microbiota |
---|---|---|---|---|
Catechins [196] | (+)-Catechin | 150 mg/mL | Ex vivo: human fecal microbiota | Increase the growth of E. rectale |
Chlorogenic acid [197] | Chlorogenic acid | 10 μg/mL | Ex vivo: human fecal microbiota | Increase the population of bifidobacterium species |
Pomegranate polyphenols [199] | Not available | 1000 mg/day | Healthy subjects | Increase the population of A. muciniphila |
Red wine [200] | 14% flavan-3-ols, 3.6% anthocyanins, 2.9% hydroxybenzoic acids | 272 mL/day | Healthy and obese subjects | Increase the proportion of F. prausnitzii in obese subjects |
Oolong tea polyphenols [202] | Catechins (88.79 μg/g) | 0.1% oolong tea polyphenols in the high-fat diet | Mice | Increase the proportion of F. prausnitzii and other SCFA-producing bacteria, as well as increase in the fecal contents of SCFAs |
Mango polyphenol extracts [40] | Gallic acid (7.35 mg/L) | ad libitum | Rats | Increase Clostridium butyrium, and improve butyrate production |
Black tea or green tea polyphenols [204] | Catechines (275 g/kg in green tea, and 35 g/kg in black tea) | 10 g/kg/day | Rats | Reduce the abundance of Clostridium XIVa |
EGCG [205] | EGCG | 0.3% in the diet | Rats | Reduce the abundance of fecal Clostridial IV and XIVa bacteria |
Polyphenolic Compounds | Effective Concentration | Detection Assay | Effect on DPP-IV Activity | Possible Mechanism |
---|---|---|---|---|
Bis-pyrano prenyl isoflavone [208] | 100 μM | DPP-4 fluorometric assay | 53% inhibition | Not available |
Rutin [209] | IC50: 0.485 mM | DPP-4 fluorometric assay | 50% inhibition | Not available |
Eriocitrin [207,209] | IC50: 5.44 mM; 10.36 ± 0.09 μM | DPP-4 fluorometric assay | 50% inhibition | H Bonds and π interactions |
Eriodictyol [209] | IC50: 3.91 mM | DPP-4 fluorometric assay | 50% inhibition | Not available |
Naringenin [207,209] | IC50: 5.5 mM; 0.24 ± 0.03 μM | DPP-4 fluorometric assay | 50% inhibition | H Bonds and π interactions |
Naringin [209] | IC50: 3.82 mM | DPP-4 fluorometric assay | 50% inhibition | Not available |
Hesperidin [209] | IC50: 5.7 mM | DPP-4 fluorometric assay | 50% inhibition | H Bonds and π interactions |
Hesperetin [207,209] | IC50: 5.7 mM; 0.28 ± 0.07 μM | DPP-4 fluorometric assay | 50% inhibition | H Bonds and π interactions |
Apigenin [207,210] | IC50: 0.14 ± 0.02 μM; 200 μM | DPP-IV GloTM Protease Assay | 50% inhibition | H Bonds and π interactions |
Quercetin [207] | IC50: 2.92 ± 0.68 μM | DPP-IV GloTM Protease Assay | 50% inhibition | H Bonds and π interactions |
Genistein [207] | IC50: 0.48 ± 0.04 μM | DPP-IV GloTM Protease Assay | 50% inhibition | H Bonds and π interactions |
Resveratrol [207,218] | IC50: 0.0006 ± 0.0004 μM | DPP-IV GloTM Protease Assay | 50% inhibition | H Bonds |
Gallic acid [207] | IC50: 4.65 ± 0.99 μM | DPP-IV GloTM Protease Assay | 50% inhibition | H Bonds and π interactions |
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Wang, Y.; Alkhalidy, H.; Liu, D. The Emerging Role of Polyphenols in the Management of Type 2 Diabetes. Molecules 2021, 26, 703. https://doi.org/10.3390/molecules26030703
Wang Y, Alkhalidy H, Liu D. The Emerging Role of Polyphenols in the Management of Type 2 Diabetes. Molecules. 2021; 26(3):703. https://doi.org/10.3390/molecules26030703
Chicago/Turabian StyleWang, Yao, Hana Alkhalidy, and Dongmin Liu. 2021. "The Emerging Role of Polyphenols in the Management of Type 2 Diabetes" Molecules 26, no. 3: 703. https://doi.org/10.3390/molecules26030703