{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:11:22Z","timestamp":1784815882945,"version":"3.55.0"},"reference-count":100,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In Diabetes Mellitus (DM), a metabolic disorder characterized by elevated blood glucose due to impaired insulin action, platelet function is dysregulated and contributes to the pathological progression of the disease. In type 2 diabetes mellitus (T2DM), hyperglycemia, insulin resistance, oxidative stress, and inflammation impair endothelial function and platelet regulation, promoting a prothrombotic state. Platelet hyperreactivity is associated with T2DM cardiovascular complications, a leading cause of mortality in patients. Antiplatelet therapies often prove ineffective for a subset of T2DM patients due to aspirin resistance, necessitating alternative therapeutic strategies. Resveratrol, a natural polyphenol, is a potential therapeutic agent for T2DM, including inhibition of platelet aggregation. One of the pleiotropic actions of resveratrol is to modulate the FoF1-ATP synthase rotational catalysis. Platelet chemical energy demand during the activation phase is achieved through oxidative phosphorylation. Both mitochondrial and extra-mitochondrial oxidative phosphorylation drive aerobic energy production in activated platelets, utilizing fatty acids and glucose, respectively. Hyperglycemia can cause an overwork of the oxidative phosphorylation, producing oxidative stress. Targeting FoF1-ATP synthase with resveratrol may reduce platelet hyperreactivity in aspirin-resistant cases. This paper reviews the implications of resveratrol ability to inhibit platelet FoF1-ATP synthase on its potential as a novel alternative or synergistic antiplatelet strategy for aspirin-resistant T2DM patients.<\/jats:p>","DOI":"10.3390\/life15111718","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:02:03Z","timestamp":1762419723000},"page":"1718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resveratrol as a Potential Platelet Inhibitor in Aspirin-Resistant Diabetic Patients\u2014A Novel Therapeutic Strategy Targeting F0F1-ATP Synthase Inhibition"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-1128","authenticated-orcid":false,"given":"Isabella","family":"Panfoli","sequence":"first","affiliation":[{"name":"Department of Pharmacy (DIFAR), University of Genoa, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-3039","authenticated-orcid":false,"given":"Lavinia","family":"Carlini","sequence":"additional","affiliation":[{"name":"Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 Diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Al Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, Regional, and National Burden of Diabetes from 1990 to 2021, with Projections of Prevalence to 2050: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"402","author":"Ong","year":"2023","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1605064","DOI":"10.3389\/ijph.2022.1605064","article-title":"System Dynamic Model Simulates the Growth Trend of Diabetes Mellitus in Chinese Population: Implications for Future Urban Public Health Governance","volume":"67","author":"Li","year":"2022","journal-title":"Int. J. Public. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global Aetiology and Epidemiology of Type 2 Diabetes Mellitus and Its Complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609213","DOI":"10.1155\/2020\/8609213","article-title":"Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus","volume":"2020","author":"Yaribeygi","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.molmet.2019.06.012","article-title":"Endoplasmic Reticulum Stress, Degeneration of Pancreatic Islet \u03b2-Cells, and Therapeutic Modulation of the Unfolded Protein Response in Diabetes","volume":"27","author":"Ghosh","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E35285","DOI":"10.1097\/MD.0000000000035285","article-title":"Vascular Complications of Diabetes: A Narrative Review","volume":"102","author":"Lu","year":"2023","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.biocel.2014.02.015","article-title":"Mitochondria: Biological Roles in Platelet Physiology and Pathology","volume":"50","author":"Oliveira","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1160\/TH17-04-0259","article-title":"Interplay between Elevated Cellular Fibronectin and Plasma Fibrin Clot Properties in Type 2 Diabetes","volume":"117","author":"Bryk","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.tem.2019.05.003","article-title":"Platelets as Potent Signaling Entities in Type 2 Diabetes Mellitus","volume":"30","author":"Pretorius","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12933-022-01516-6","article-title":"Cardiovascular Disease in Type 2 Diabetes Mellitus: Progress toward Personalized Management","volume":"21","author":"Ma","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1161\/CIRCULATIONAHA.116.023164","article-title":"Aspirin for Primary Cardiovascular Risk Prevention and Beyond in Diabetes Mellitus","volume":"134","author":"Capodanno","year":"2016","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41392-025-02198-8","article-title":"Platelets and Diseases: Signal Transduction and Advances in Targeted Therapy","volume":"10","author":"Tian","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, L.X., Li, C.X., Kakar, M.U., Khan, M.S., Wu, P.F., Amir, R.M., Dai, D.F., Naveed, M., Li, Q.Y., and Saeed, M. (2021). Resveratrol (RV): A Pharmacological Review and Call for Further Research. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112164"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.aca.2008.12.003","article-title":"Simple Spectrophotometric Assessment of the Trans-\/Cis-Resveratrol Ratio in Aqueous Solutions","volume":"634","author":"Camont","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/nyas.12198","article-title":"Interplay between Metabolism and Transport of Resveratrol","volume":"1290","author":"Riha","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/mnfr.200500002","article-title":"Bioavailability of Trans-Resveratrol from Red Wine in Humans","volume":"49","author":"Vitaglione","year":"2005","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/ptr.8379","article-title":"Resveratrol Bioavailability After Oral Administration: A Meta-Analysis of Clinical Trial Data","volume":"39","author":"Szymkowiak","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"837042","DOI":"10.1155\/2015\/837042","article-title":"Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans","volume":"2015","author":"Gambini","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2165\/11531820-000000000-00000","article-title":"Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000 Mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects","volume":"49","author":"Voduc","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1182\/blood-2014-08-531582","article-title":"Platelets at the Interface of Thrombosis, Inflammation, and Cancer","volume":"126","author":"Franco","year":"2015","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.blre.2011.03.002","article-title":"Platelets at Work in Primary Hemostasis","volume":"25","author":"Broos","year":"2011","journal-title":"Blood Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100694","DOI":"10.1016\/j.blre.2020.100694","article-title":"Platelet Activation and Prothrombotic Mediators at the Nexus of Inflammation and Atherosclerosis: Potential Role of Antiplatelet Agents","volume":"45","author":"Lordan","year":"2021","journal-title":"Blood Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1177\/09760016251317265","article-title":"Platelet Indices as Predictors of Glycaemic Status and Complications in Diabetes Mellitus","volume":"22","author":"Jena","year":"2025","journal-title":"Apollo Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1111\/j.1538-7836.2007.02728.x","article-title":"Persistent Platelet Activation in Patients with Type 2 Diabetes Treated with Low Doses of Aspirin","volume":"5","author":"Evangelista","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12933-018-0783-z","article-title":"Platelet Activity and Hypercoagulation in Type 2 Diabetes","volume":"17","author":"Pretorius","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26009","DOI":"10.31083\/RCM26009","article-title":"Clinical Predictors of Aspirin Resistance in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis","volume":"26","author":"Zhang","year":"2025","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12933-018-0763-3","article-title":"Endothelial Dysfunction and Platelet Hyperactivity in Type 2 Diabetes Mellitus: Molecular Insights and Therapeutic Strategies","volume":"17","author":"Kaur","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1007\/s00125-025-06429-z","article-title":"Insulin Resistance in Type 1 Diabetes Is a Key Modulator of Platelet Hyperreactivity","volume":"68","author":"Sagar","year":"2025","journal-title":"Diabetologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102623","DOI":"10.1016\/j.rpth.2024.102623","article-title":"Stability of the Thromboxane B2 Biomarker of Low-Dose Aspirin Pharmacodynamics in Human Whole Blood and in Long-Term Stored Serum Samples","volume":"8","author":"Petrucci","year":"2024","journal-title":"Res. Pr. Thromb. Haemost."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1182\/blood.V110.11.3896.3896","article-title":"Is the New Point-of-Care Test VerifyNow\u00ae Aspirin Able To Identify Aspirin Resistance Using the Recommended Cut-Off?","volume":"110","author":"Nielsen","year":"2007","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/j.1538-7836.2008.02897.x","article-title":"Use of the PFA-100TM Closure Time to Predict Cardiovascular Events in Aspirin-Treated Cardiovascular Patients: A Systematic Review and Meta-Analysis","volume":"6","author":"Reny","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.3324\/haematol.2010.027102","article-title":"Inconsistency of Different Methods for Assessing Ex Vivo Platelet Function: Relevance for the Detection of Aspirin Resistance","volume":"95","author":"Renda","year":"2010","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"742719","DOI":"10.1155\/2011\/742719","article-title":"Platelet Function in Patients with Diabetes Mellitus: From a Theoretical to a Practical Perspective","volume":"2011","author":"Kakouros","year":"2011","journal-title":"Int. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1111\/j.1538-7836.2008.03185.x","article-title":"Platelet Hyperprocoagulant Activity in Type 2 Diabetes Mellitus: Attenuation by Glycoprotein IIb\/IIIa Inhibition","volume":"6","author":"Razmara","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.thromres.2011.12.002","article-title":"Platelet Oxidative Stress and Thrombosis","volume":"129","author":"Violi","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/CIRCULATIONAHA.116.026995","article-title":"Platelets Express Activated P2Y12 Receptor in Patients with Diabetes Mellitus","volume":"136","author":"Hu","year":"2017","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S179","DOI":"10.2337\/dc24-S010","article-title":"10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes\u20142024","volume":"47","author":"Committee","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/dme.12828","article-title":"Randomized Controlled Trial Comparing Impact on Platelet Reactivity of Twice-Daily with Once-Daily Aspirin in People with Type 2 Diabetes","volume":"33","author":"Bethel","year":"2016","journal-title":"Diabet. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ahj.2025.04.016","article-title":"Twice-a-Day Administration of Aspirin in Patients with Diabetes Mellitus or Aspirin Resistance after Acute Coronary Syndrome: Rationale and Design of the Randomized ANDAMAN Trial","volume":"288","author":"Dillinger","year":"2025","journal-title":"Am. Heart J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2337\/dc23-0749","article-title":"Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial","volume":"47","author":"Narcisse","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vaidya, A.R., Wolska, N., Vara, D., Mailer, R.K., Schr\u00f6der, K., and Pula, G. (2021). Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress. Antioxidants, 10.","DOI":"10.3390\/antiox10050706"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C719","DOI":"10.1152\/ajpcell.2001.280.4.C719","article-title":"Oxidant Stress and Endothelial Cell Dysfunction","volume":"280","author":"Lum","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_47","first-page":"4599","article-title":"Diabetes and Platelet Response to Low-Dose Aspirin","volume":"103","author":"Yanek","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Duttaroy, A.K. (2024). Functional Foods in Preventing Human Blood Platelet Hyperactivity-Mediated Diseases-An Updated Review. Nutrients, 16.","DOI":"10.20944\/preprints202410.0294.v1"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3892\/mi.2024.191","article-title":"Recent Advances in the Use of Resveratrol against Staphylococcus Aureus Infections (Review)","volume":"4","author":"Cui","year":"2024","journal-title":"Med. Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Su, M., Zhao, W., Xu, S., and Weng, J. (2022). Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action. Antioxidants, 11.","DOI":"10.3390\/antiox11061085"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9731","DOI":"10.29219\/fnr.v68.9731","article-title":"Potential Role of Resveratrol in Prevention and Therapy of Diabetic Complications: A Critical Review","volume":"68","author":"Koushki","year":"2024","journal-title":"Food Nutr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1111\/j.1755-3768.2011.02243.x","article-title":"Resveratrol Blocks Diabetes-Induced Early Vascular Lesions and Vascular Endothelial Growth Factor Induction in Mouse Retinas","volume":"90","author":"Kim","year":"2012","journal-title":"Acta Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ka\u0161telan, S., Konjevoda, S., Sari\u0107, A., Urli\u0107, I., Lovri\u0107, I., \u010canovi\u0107, S., Mateji\u0107, T., and \u0160e\u0161elja Peri\u0161in, A. (2025). Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges. Molecules, 30.","DOI":"10.3390\/molecules30153262"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/bjh.13862","article-title":"Resveratrol Preserves the Function of Human Platelets Stored for Transfusion","volume":"172","author":"Lannan","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Michno, A., Gru\u017cewska, K., Ronowska, A., Gul-Hinc, S., Zy\u015bk, M., and Jankowska-Kulawy, A. (2022). Resveratrol Inhibits Metabolism and Affects Blood Platelet Function in Type 2 Diabetes. Nutrients, 14.","DOI":"10.3390\/nu14081633"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s13167-022-00293-2","article-title":"Antithrombotic and Antiplatelet Effects of Plant-Derived Compounds: A Great Utility Potential for Primary, Secondary, and Tertiary Care in the Framework of 3P Medicine","volume":"13","author":"Kubatka","year":"2022","journal-title":"EPMA J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105725","DOI":"10.1016\/j.phrs.2021.105725","article-title":"Resveratrol and Endothelial Function: A Literature Review","volume":"170","author":"Parsamanesh","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.phrs.2016.08.010","article-title":"Six Months of Resveratrol Supplementation Has No Measurable Effect in Type 2 Diabetic Patients. A Randomized, Double Blind, Placebo-Controlled Trial","volume":"111","author":"Bo","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"102819","DOI":"10.1016\/j.ctim.2022.102819","article-title":"Role of Resveratrol Supplementation in Regulation of Glucose Hemostasis, Inflammation and Oxidative Stress in Patients with Diabetes Mellitus Type 2: A Randomized, Placebo-Controlled Trial","volume":"66","author":"Mahjabeen","year":"2022","journal-title":"Complement. Ther. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00592-017-0977-y","article-title":"Effects of 6 Months of Resveratrol versus Placebo on Pentraxin 3 in Patients with Type 2 Diabetes Mellitus: A Double-Blind Randomized Controlled Trial","volume":"54","author":"Bo","year":"2017","journal-title":"Acta Diabetol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.2337\/dc16-0499","article-title":"Resveratrol as Add-on Therapy in Subjects with Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial","volume":"39","author":"Timmers","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3945\/ajcn.115.117440","article-title":"Administration of Resveratrol for 5 Wk Has No Effect on Glucagon-like Peptide 1 Secretion, Gastric Emptying, or Glycemic Control in Type 2 Diabetes: A Randomized Controlled Trial","volume":"103","author":"Thazhath","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1002\/ptr.6487","article-title":"The Effect of Resveratrol Supplementation on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double-Blind Controlled Trial","volume":"33","author":"Abdollahi","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s00592-018-1160-9","article-title":"Correction to: The Effects of Resveratrol on Markers of Oxidative Stress in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"55","author":"Seyyedebrahimi","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.1039\/C9FO01075K","article-title":"The Effects of Resveratrol on Metabolic Status in Patients with Type 2 Diabetes Mellitus and Coronary Heart Disease","volume":"10","author":"Hoseini","year":"2019","journal-title":"Food Funct."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Mart\u00ednez, B.I., Ruiz-Ramos, M., Pedraza-Chaverri, J., Santiago-Osorio, E., and Mendoza-N\u00fa\u00f1ez, V.M. (2023). Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087422"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Mart\u00ednez, B.I., Ruiz-Ramos, M., Pedraza-Chaverri, J., Santiago-Osorio, E., and Mendoza-N\u00fa\u00f1ez, V.M. (2022). Influence of Age and Dose on the Effect of Resveratrol for Glycemic Control in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis. Molecules, 27.","DOI":"10.3390\/molecules27165232"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Zhu, P., Jin, Y., Sun, J., and Zhou, X. (2025). The Efficacy of Resveratrol Supplementation on Inflammation and Oxidative Stress in Type-2 Diabetes Mellitus Patients: Randomized Double-Blind Placebo Meta-Analysis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1463027"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E30049","DOI":"10.1097\/MD.0000000000030049","article-title":"Effects of Resveratrol Therapy on Glucose Metabolism, Insulin Resistance, Inflammation, and Renal Function in the Elderly Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Clinical Trial Protocol","volume":"101","author":"Ma","year":"2022","journal-title":"Medicine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20110773","article-title":"The ATP Synthase: The Understood, the Uncertain and the Unknown","volume":"41","author":"Walker","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1146\/annurev.biochem.66.1.717","article-title":"The ATP Synthase\u2014A Splendid Molecular Machine","volume":"66","author":"Boyer","year":"1997","journal-title":"Annu. Rev. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cmet.2008.06.001","article-title":"Regulation of Mitochondrial Structure and Function by the F1Fo-ATPase Inhibitor Protein, IF1","volume":"8","author":"Campanella","year":"2008","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R245","DOI":"10.1093\/hmg\/ddab156","article-title":"Mitochondrial DNA Disorders: From Pathogenic Variants to Preventing Transmission","volume":"30","author":"Ng","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1586\/epr.11.1","article-title":"Proteomics Unravels the Exportability of Mitochondrial Respiratory Chains","volume":"8","author":"Panfoli","year":"2011","journal-title":"Expert. Rev. Proteomics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature01250","article-title":"Ectopic Beta-Chain of ATP Synthase Is an Apolipoprotein A-I Receptor in Hepatic HDL Endocytosis","volume":"421","author":"Martinez","year":"2003","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1074\/mcp.RA120.002219","article-title":"Multiomics Reveals Ectopic ATP Synthase Blockade Induces Cancer Cell Death via a LncRNA-Mediated Phospho-Signaling Network","volume":"19","author":"Chang","year":"2020","journal-title":"Mol. Cell Proteom."},{"key":"ref_77","first-page":"704","article-title":"Direct Targeting of Tumor Cell F(1)F(0) ATP-Synthase by Radioiodine Angiostatin In Vitro and In Vivo","volume":"22","author":"Jung","year":"2007","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1021\/pr0601739","article-title":"Proteomic Analysis of Plasma Membrane from Hypoxia-Adapted Malignant Melanoma","volume":"5","author":"Stockwin","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"H1646","DOI":"10.1152\/ajpheart.01385.2006","article-title":"Involvement of Cell Surface ATP Synthase in Flow-Induced ATP Release by Vascular Endothelial Cells","volume":"293","author":"Yamamoto","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_80","first-page":"931","article-title":"Possible Role of Cell Surface H+ -ATP Synthase in the Extracellular ATP Synthesis and Proliferation of Human Umbilical Vein Endothelial Cells","volume":"1","author":"Arakaki","year":"2003","journal-title":"Mol. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.bbabio.2008.08.003","article-title":"Structural and Functional Characterization of FoF1-ATP Synthase on the Extracellular Surface of Rat Hepatocytes","volume":"1777","author":"Mangiullo","year":"2008","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_82","first-page":"81","article-title":"Neuronal Cell Surface ATP Synthase Mediates Synthesis of Extracellular ATP and Regulation of Intracellular PH","volume":"35","author":"Xing","year":"2011","journal-title":"Cell Biol. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1002\/jnr.24865","article-title":"Efficient Extra-Mitochondrial Aerobic ATP Synthesis in Neuronal Membrane Systems","volume":"99","author":"Ravera","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1096\/fj.15-279679","article-title":"Exosomes from Human Mesenchymal Stem Cells Conduct Aerobic Metabolism in Term and Preterm Newborn Infants","volume":"30","author":"Panfoli","year":"2016","journal-title":"FASEB J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1700082","DOI":"10.1002\/prca.201700082","article-title":"Metabolic Signature of Microvesicles from Umbilical Cord Mesenchymal Stem Cells of Preterm and Term Infants","volume":"12","author":"Bruschi","year":"2018","journal-title":"Proteom. Clin. Appl."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/boc.201700025","article-title":"Extramitochondrial Energy Production in Platelets","volume":"110","author":"Ravera","year":"2018","journal-title":"Biol. Cell"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ravera, S., Signorello, M.G., and Panfoli, I. (2023). Platelet Metabolic Flexibility: A Matter of Substrate and Location. Cells, 12.","DOI":"10.3390\/cells12131802"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, J., Li, D., Zhou, L., Li, Y., Xi, Q., Zhang, L., and Zhang, J. (2025). The Role of Mitochondria-Associated ER Membranes in Disease Pathology: Protein Complex and Therapeutic Targets. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1629568"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3324\/haematol.2018.205724","article-title":"Aerobic Glycolysis Fuels Platelet Activation: Small-Molecule Modulators of Platelet Metabolism as Anti-Thrombotic Agents","volume":"104","author":"Kulkarni","year":"2019","journal-title":"Haematologica"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155596","DOI":"10.1016\/j.metabol.2023.155596","article-title":"Energy Metabolism in Platelets Fuels Thrombus Formation: Halting the Thrombosis Engine with Small-Molecule Modulators of Platelet Metabolism","volume":"145","author":"Kulkarni","year":"2023","journal-title":"Metabolism"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1111\/jth.14274","article-title":"Glucose Metabolism and Metabolic Flexibility in Blood Platelets","volume":"16","author":"Aibibula","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1050962","DOI":"10.3109\/10715762.2015.1050962","article-title":"Oxidative Stress in Myelin Sheath: The Other Face of the Extramitochondrial Oxidative Phosphorylation Ability","volume":"49","author":"Ravera","year":"2015","journal-title":"Free Radic. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.2337\/diabetes.50.6.1491","article-title":"Hyperglycemia Potentiates Collagen-Induced Platelet Activation through Mitochondrial Superoxide Overproduction","volume":"50","author":"Yamagishi","year":"2001","journal-title":"Diabetes"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.lfs.2016.02.030","article-title":"Higher Mitochondrial Potential and Elevated Mitochondrial Respiration Are Associated with Excessive Activation of Blood Platelets in Diabetic Rats","volume":"148","author":"Siewiera","year":"2016","journal-title":"Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Carlini, L., Tancreda, G., Iobbi, V., Caicci, F., Bruno, S., Esposito, A., Calzia, D., Benini, S., Bisio, A., and Manni, L. (2022). The Flavone Cirsiliol from Salvia x Jamensis Binds the F1 Moiety of ATP Synthase, Modulating Free Radical Production. Cells, 11.","DOI":"10.3390\/cells11193169"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.jsps.2015.03.013","article-title":"Diabetes Mellitus and Oxidative Stress\u2014A Concise Review","volume":"24","author":"Asmat","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2016.04.001","article-title":"Mitochondrial Generation of Superoxide and Hydrogen Peroxide as the Source of Mitochondrial Redox Signaling","volume":"100","author":"Brand","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_98","first-page":"126","article-title":"Mitochondrial Dysfunction: Mechanisms and Advances in Therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1038\/s41467-023-37351-w","article-title":"Mitochondrial ATP Synthase as a Direct Molecular Target of Chromium(III) to Ameliorate Hyperglycaemia Stress","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/MOL.0000000000000434","article-title":"Serum Inhibitory Factor 1, High-Density Lipoprotein and Cardiovascular Diseases","volume":"28","author":"Martinez","year":"2017","journal-title":"Curr. Opin. Lipidol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:25:46Z","timestamp":1762421146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":100,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["life15111718"],"URL":"https:\/\/doi.org\/10.3390\/life15111718","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}