{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:06:40Z","timestamp":1783919200493,"version":"3.55.0"},"reference-count":62,"publisher":"Korean Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270520"],"award-info":[{"award-number":["82270520"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YCJJ20230687"],"award-info":[{"award-number":["YCJJ20230687"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>Background: Diabetic foot ulcer (DFU) is a challenging complication of diabetes mellitus, characterized by delayed wound healing. Protein kinase C delta (PKC\u03b4) has been identified as an important factor in the pathogenesis of various diabetic complications, including DFU. However, the precise underlying mechanisms remain incompletely elucidated.Methods: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions, and PKC\u03b4 was knocked down using siRNA. The proliferation, migration, and tube formation of HUVECs were assessed. Metabolomic sequencing was performed to identify potential metabolites contributing to these changes. HUVEC proliferation, migration, tube formation, and apoptosis were then assessed after regulation of the selected metabolite. Finally, the effect of the metabolite on diabetic wound healing was evaluated.Results: In vitro, PKC\u03b4 knockdown upregulated glutamate decarboxylase 1 (GAD1) expression and gamma-aminobutyric acid (GABA) levels, which enhanced proliferation, migration, and tube formation and suppressed apoptosis of HUVECs under high glucose conditions. Interestingly, inhibition of GAD1 in normal glucose-treated HUVECs decreased proliferation, migration, and tube formation, and increased apoptosis. Furthermore, in vivo experiments demonstrated that topical administration of GABA accelerated the healing of diabetic wounds in streptozotocin-induced type 2 diabetes mellitus mice, as manifested by increased angiogenesis and proliferation.Conclusion: PKC\u03b4-mediated inhibition of the GAD1-GABA pathway suppresses endothelial cell proliferation, migration, and tube formation and promotes apoptosis under high-glucose conditions, thereby delaying diabetic wound healing.<\/jats:p>","DOI":"10.4093\/dmj.2024.0450","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T07:53:36Z","timestamp":1757318016000},"page":"688-706","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Abnormally Elevated PKC\u03b4 Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA 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