The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide presents significant challenges in the management of impaired tissue repair in diabetic skin wounds, which has emerged as a critical health concern. Addressing this issue while minimizing adverse effects remains crucial. Allulose has been shown to exhibit hypolipidemic and anti-inflammatory properties, alleviating obesity and atherosclerosis by improving insulin resistance and impaired glucose tolerance. However, its underlying effects and mechanisms in repairing diabetic skin damage remain poorly understood. In this study, we demonstrated that oral administration of allulose remarkably ameliorated T2DM-compromised skin tissue wound associated with the stimulation of skin granulation, surrounding tissue formation, and activated fibroblasts, under high-fat diet (HFD) feeding condition. In addition, administration partially promoted collagen deposition, reduced M1 macrophage polarization, facilitated neovascularization, and mitigated tissue inflammation in the T2DM rats upon HFD feeding. Moreover, allulose could significantly alleviate high glucose stress condition-induced inflammatory response, correlative with modulation of p38/NLRP3/Caspase-1 signaling. In addition, allulose could also ameliorate high glucose stress-compromised cell viability and proliferative capacity, related to stimulation of mTOR pathway in part. Taken together, our study revealed that T2DM compromised some certain factors which are crucial for skin tissue healing and wound repair upon HFD condition. The work highlighted the potential beneficial effects of orally administered allulose for healing diabetic skin wounds and supported a novel strategy for managing diabetes patients adjunctively with allulose dietary supplement.
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