Omentin-1 promotes wound healing in diabetic mice by improving vascular endothelial cell function

Diabetes is a metabolic disease that affects global human health, with 25% of diabetic patients suffering from chronic non-healing ulcers. Omentin-1, also referred to as intelectin-1 and encoded by the itln1 gene, is a recently discovered adipokine that modulates inflammation, cellular activities, and vascular tone. Research indicates that omentin-1 provides protective benefits in several conditions, including atherosclerosis and diabetic retinopathy. Nevertheless, the therapeutic potential of omentin-1 in promoting diabetic wound healing is still not well understood. Our results revealed a significant decrease in ITLN1 levels in the cutaneous tissues of diabetic mice. Subcutaneous injection of omentin-1 reduced endothelial cell apoptosis, enhanced angiogenesis, and accelerated wound repair in diabetic mice. In vitro studies demonstrated that omentin-1 upregulated VEGF expression in endothelial cells, improved endothelial function under high-glucose conditions, reduced high glucose-induced endothelial apoptosis, and promoted endothelial tube formation. Further mechanistic studies revealed that omentin-1 improved endothelial function and promoted angiogenesis under high-glucose conditions by mediating the PI3K/AKT/FOXO1 pathway. Our results suggest that omentin-1 is a potential adjunct or therapeutic agent for treating chronic non-healing diabetic wounds by enhancing endothelial cell function and promoting vascularization.