Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats

dc.authorscopusidFatma Kübra Tombultürk / 56748052500
dc.authorwosidFatma Kübra Tombultürk / L-3969-2018
dc.contributor.authorTombultürk, Fatma Kübra
dc.contributor.authorSoydaş, Tuğba
dc.contributor.authorKanigür Sultuybek, Gönül
dc.date.accessioned2025-04-18T10:28:42Z
dc.date.available2025-04-18T10:28:42Z
dc.date.issued2024
dc.departmentİstinye Üniversitesi, Sağlık Hizmetleri Meslek Yüksekokulu, Tıbbi Laboratuvar Teknikleri Programı
dc.description.abstractThe molecular mechanisms underlying delayed wound repair in diabetes involve dysregulation of key cellular processes, including autophagy and hypoxia response pathways. Herein, we investigated the role of topical metformin, an established anti-diabetic drug with potential autophagy-inducing properties, in improving wound healing outcomes under hypoxic conditions. Full-thickness skin wounds were created in streptozotocin-induced diabetic rats, and tissue samples were collected at regular intervals for molecular and histological analysis. The expression levels of autophagy markers LC3B and Beclin-1 were evaluated via immunohistochemistry and qRT-PCR, while the amount of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) were determined via ELISA. Our results demonstrated that metformin administration resulted in the upregulation of LC3B and Beclin-1 in the wound bed, suggesting induction of autophagy in response to the treatment. Mechanistically, metformin treatment also led to the increased amount of AMPK, a critical regulator of cellular energy homeostasis, and a subsequent reduction in HIF-1α amount under hypoxic conditions. In conclusion, our findings demonstrate that metformin promotes wound healing in diabetes mellitus by enhancing autophagy through AMPK activation and modulating HIF-1α amount in a hypoxic microenvironment. This study offers a new therapeutic approach by shedding light on the potential benefits of metformin as adjunctive therapy in diabetic wound management. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
dc.description.sponsorshipThis study was funded by The Scientific and Technological Research Council of Turkey (TUBITAK) (grant number 120S628).
dc.identifier.citationTombulturk, F. K., Soydas, T., & Kanigur-Sultuybek, G. (2024). Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats. Inflammation, 1-12.
dc.identifier.doi10.1007/s10753-024-02129-9
dc.identifier.issn03603997
dc.identifier.scopus2-s2.0-85202077741
dc.identifier.scopusqualityQ1
dc.identifier.urihttp://dx.doi.org/10.1007/s10753-024-02129-9
dc.identifier.urihttps://hdl.handle.net/20.500.12713/7083
dc.identifier.wosWOS:001297782200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakScopus
dc.indekslendigikaynakWeb of Science
dc.institutionauthorTombultürk, Fatma Kübra
dc.institutionauthoridFatma Kübra Tombultürk / 0000-0002-4358-2309
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofInflammation
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitak120S628
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAMPK
dc.subjectAutophagy
dc.subjectDiabetes Mellitus
dc.subjectHypoxia
dc.subjectMetformin
dc.subjectWound Healing
dc.titleMetformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats
dc.typeArticle

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