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https://www.selleckchem.com/products/bms-986278.html BACKGROUND β-cell dysfunction is one of the core pathogenetic mechanisms of type 2 diabetes mellitus (T2DM). However, there are currently no effective therapeutic strategies to preserve β-cell mass and function. The role of islet macrophage phenotype reprogramming in β-cell dysfunction has attracted great attention. Given that advanced glycation end products (AGEs) are major pathogenic factors in T2DM, we investigated the effect of AGEs on macrophage activation and their role in β-cell dysfunction. METHODS We examined cytokine secretion, M1 and M2 macrophage-associated marker expression and MAPK phosphorylation levels in AGEs-stimulated macrophages. MIN6 cells were cocultured with AGEs-pretreated macrophages to study the effect of AGEs-induced macrophage activation on β-cell dysfunction. RESULTS We found that AGEs treatment significantly enhanced macrophage secretion of proinflammatory cytokines. The expression of M1 macrophage markers, such as iNOS and the surface marker CD11c, was significantly upregulated, whereas the expression of M2 macrophage markers, such as Arg1 and CD206, was reciprocally downregulated upon AGEs stimulation. AGEs treatment predominantly activated the MAPK pathway, and the inhibition of the MAPK pathway partially attenuated the AGEs-induced polarization of macrophages. In addition, coculture with AGEs-pretreated macrophages significantly inhibited the expression of molecules involved in β-cell function and was accompanied by the impairment of glucose-stimulated insulin secretion (GSIS) in MIN6 cells. CONCLUSION AGEs enhance the expression of proinflammatory molecules by activating the MAPK pathway. Moreover, these data imply that AGEs induce macrophage M1 phenotype polarization but restrain M2 polarization, which might contribute to β-cell dysfunction in the pathogenesis of T2DM. Skeletal muscle is divided into type 1 and type 2 fibers. Type 1 fibers are rich in mitochondria, have high oxi

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