Dual mechanistic role of polyphenols in modulating the insulin-related metabolic pathways: insights from computer-aided analysis

Dual mechanistic role of polyphenols in modulating the insulin-related metabolic pathways: insights from computer-aided analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dual mechanistic role of polyphenols in modulating the insulin-related metabolic pathways: insights from computer-aided analysis Valeriya M. Trusova, Uliana K. Malovytsia, Mette Hedegaard Thomsen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9036557/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Apr, 2026 Read the published version in Cell Biochemistry and Biophysics → Version 1 posted 14 You are reading this latest preprint version Abstract The intricate computer-aided analysis has been employed to investigate the different aspects of insulin cooperation with polyphenols, including quercetin, resveratrol, sesamin, gallic and salicylic acids. Molecular docking and molecular dynamics simulations revealed that quercetin, resveratrol and sesamin binding to the insulin via hotspot amino acid residues Phe24-Tyr26 results in opening of protein structure and stabilization of Phe24, the steps which are critical for initiating the insulin binding to its receptor. Network pharmacology analysis coupled with bioactivity and toxicity predictions underscored the potential of quercetin, resveratrol and gallic acid to interact with pivotal insulin metabolic pathways, namely, AMPK and mTOR. The revealed capability of quercetin and resveratrol to alter directly the structure of insulin coupled with their ability to modify protein metabolic pathways, underscores the dual positive mechanistic influence these polyphenols have in the management of insulin-centric impairments. insulin polyphenols molecular docking molecular dynamics network pharmacology Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Apr, 2026 Read the published version in Cell Biochemistry and Biophysics → Version 1 posted Editorial decision: Revision requested 30 Mar, 2026 Reviews received at journal 25 Mar, 2026 Reviewers agreed at journal 12 Mar, 2026 Reviewers agreed at journal 09 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviewers agreed at journal 08 Mar, 2026 Reviewers agreed at journal 07 Mar, 2026 Reviewers agreed at journal 07 Mar, 2026 Reviewers agreed at journal 06 Mar, 2026 Reviewers agreed at journal 06 Mar, 2026 Reviewers invited by journal 06 Mar, 2026 Editor assigned by journal 05 Mar, 2026 Submission checks completed at journal 05 Mar, 2026 First submitted to journal 05 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9036557","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":603460264,"identity":"aaf19f8f-c12c-4638-8f54-8f40377b46bf","order_by":0,"name":"Valeriya M. 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