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Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review

Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We...

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Autores principales: Nie, Tina, Cooper, Garth J. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712966/
https://www.ncbi.nlm.nih.gov/pubmed/34970150
http://dx.doi.org/10.3389/fphar.2021.798329
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author Nie, Tina
Cooper, Garth J. S.
author_facet Nie, Tina
Cooper, Garth J. S.
author_sort Nie, Tina
collection PubMed
description Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes.
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spelling pubmed-87129662021-12-29 Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review Nie, Tina Cooper, Garth J. S. Front Pharmacol Pharmacology Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712966/ /pubmed/34970150 http://dx.doi.org/10.3389/fphar.2021.798329 Text en Copyright © 2021 Nie and Cooper. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Nie, Tina
Cooper, Garth J. S.
Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title_full Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title_fullStr Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title_full_unstemmed Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title_short Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review
title_sort mechanisms underlying the antidiabetic activities of polyphenolic compounds: a review
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712966/
https://www.ncbi.nlm.nih.gov/pubmed/34970150
http://dx.doi.org/10.3389/fphar.2021.798329
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