{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:30:55Z","timestamp":1783344655268,"version":"3.54.6"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Piau\u00ed","award":["#026\/2019"],"award-info":[{"award-number":["#026\/2019"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Piau\u00ed","award":["#315096\/2023-3"],"award-info":[{"award-number":["#315096\/2023-3"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["#026\/2019"],"award-info":[{"award-number":["#026\/2019"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["#315096\/2023-3"],"award-info":[{"award-number":["#315096\/2023-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Bioactive peptides derived from animal venoms, toxins, and secretions demonstrate considerable pharmacological potential for use in the management of diabetes mellitus\u2014a highly prevalent metabolic disorder of substantial global health significance. This integrative review systematically evaluated the current evidence regarding the pharmacological mechanisms underlying the antidiabetic properties of these bioactive peptides. Methods: This study was guided by the research question \u201cWhat are the mechanisms of action of peptides derived from animal venoms in modulating parameters associated with diabetes?\u201d developed using the PECo framework. A comprehensive literature search was executed across Scopus, PubMed, and Web of Science, focusing on studies from the last five years. Out of 190 identified articles, 17 satisfied the inclusion criteria. Results: Twenty-eight distinct peptides were characterized, exhibiting structural diversity with 7\u2013115 amino acid residues and molecular weights of 900\u201313,000 Da. These compounds were sourced from venomous taxa including sea anemones, marine snails, spiders, centipedes, scorpions, and snakes. Their antidiabetic mechanisms encompassed glucagon-like peptide-1 (GLP-1) receptor agonism, insulin receptor activation, potassium channel inhibition, glucose transporter type 4 (GLUT4) upregulation, and \u03b1-amylase inhibition. Sequence analyses revealed substantial homology among peptides with analogous mechanisms\u2014notably Con-Ins and ILP-Ap04, plus SpTx1 and SsTx-4\u2014suggesting that structural determinants underlie their functional characteristics. Toxicological evaluations of nine peptides demonstrated low-toxicity profiles despite originating from toxic venom, crucial for therapeutic development. Conclusions: These peptides exhibited exceptional pharmacological potency with effective doses in nanogram-to-nanomole per kilogram ranges. Collectively, our findings underscore the therapeutic potential of venom-derived peptides as innovative candidates for use in diabetes management.<\/jats:p>","DOI":"10.3390\/ph18101438","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:05:13Z","timestamp":1758801913000},"page":"1438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peptides from Animal Venoms: A Promising Frontier in Diabetes Therapy via Multi-Target Mechanisms"],"prefix":"10.3390","volume":"18","author":[{"given":"Jos\u00e9 Ot\u00e1vio Carvalho Sena","family":"de Almeida","sequence":"first","affiliation":[{"name":"LAFMOL\u2013Laboratory of Functional and Molecular Studies in Physiopharmacology, Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, Brazil"},{"name":"Graduate School of Pharmacology\u2013PPGFarm, Medicinal Plants Research Center, Federal University of Piaui, Ministro Petr\u00f4nio Portella Campus, Teresina 64049-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-694X","authenticated-orcid":false,"given":"Sim\u00f3n Gabriel","family":"Comerma-Steffensen","sequence":"additional","affiliation":[{"name":"Pulmonary and Cardiovascular Pharmacology, Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Animal Physiology, Department of Biomedical Sciences, Faculty of Veterinary, Central University of Venezuela, Maracay 2105, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1096-3236","authenticated-orcid":false,"given":"Jos\u00e9 Roberto","family":"de Souza de Almeida Leite","sequence":"additional","affiliation":[{"name":"Research Group in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-7666","authenticated-orcid":false,"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Pulmonary and Cardiovascular Pharmacology, Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-2744","authenticated-orcid":false,"given":"Daniel Dias Rufino","family":"Arcanjo","sequence":"additional","affiliation":[{"name":"LAFMOL\u2013Laboratory of Functional and Molecular Studies in Physiopharmacology, Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, Brazil"},{"name":"Graduate School of Pharmacology\u2013PPGFarm, Medicinal Plants Research Center, Federal University of Piaui, Ministro Petr\u00f4nio Portella Campus, Teresina 64049-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/03007995.2024.2333440","article-title":"Diabetes: A review of its pathophysiology, and advanced methods of mitigation","volume":"40","author":"Gupta","year":"2024","journal-title":"Curr. 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