Introduction and Objective: The critical role of innate immune activation leading to inflammatory events in the body has become of much interest and investigation in recent times because of its strategic importance in diabetes pathophysiology. Therefore, therapeutic targeting of innate immune activation may provide a new approach to treatment/management of diabetes. Carnosine is a physiological dipeptide consisting of β-alanine and L-histidine with emerging anti-diabetic potential. We investigated anti-inflammatory actions of carnosine in mitigating macrophage activation and glucolipotoxicity-mediated inflammation in pancreatic β-cells.Methods: Macrophages derived from human monocytes were exposed to LPS/IFNγ media supplemented with or without carnosine for 24 hrs. Cytokines were quantified in the cell supernatants using Bio-Plex Pro Human17-plex Assay. Cellular oxidative level was also measured. Additionally, pancreatic β-cells were exposed to glucolipotoxic (GLT) levels of glucose, palmitic and oleic acids supplemented with or without carnosine for 5 days. Expression level of key proteins in macrophage activation pathways and pro-inflammatory regulation in pancreatic β-cells were also investigated.Results: Carnosine suppressed both LPS/IFNy-mediated macrophage activation and GLT-induced inflammation in β-cells with evident decrease in nuclear localization of NF-κΒ. In addition, carnosine blocked TNFR5/CD40 signaling pathways to mitigate inflammation in β-cells. Also, COX-2, STAT1 and TLR2 protein expression levels were all reduced by carnosine, with subsequent decrease in cellular oxidative stress. Importantly, carnosine significantly reduced the levels of pro-inflammatory cytokines (G-CSF, GM-CSF, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-7, TNF-α, IL-17A, IL-12 and MCP-1) released from activated macrophages.Conclusion: This data provides evidence of strong anti-inflammatory potential of carnosine, which could be beneficial in the treatment/management of diabetes.
J.N. Awoke: None. S. Colombo: None. C. Sale: Research Support; Natural Alternatives International. M.D. Turner: None.
Commonwealth Scholarship Commission in the UK
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