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Local production of reactive oxygen species (ROS) and changes in the redox environment influence the metabolism and function of β cells of the Langerhans islets (LO). Changing the ratio between NAD(P)H / NAD(P)+ redox partners significantly affects sensitive proteins and ROS production. ROS are able to reversibly modify some amino acid residues (eg Cys, Met) of antioxidant enzymes and their interaction partners. Such a signaling cascade allows the transmission of a signal over longer distances and can also interfere with the influence of gene expression. The unique enzyme NADPH oxidase 4 (NOX4) is present on membranes within β cells and constitutively produces H2O2 depending on the presence of NAD(P)H. After glucose stimulation, both NAD(P)H and Nox4 mRNA levels increase. As previously observed in our laboratory, C57BL/6J mice with a specific Nox4 deletion in β cells have a disrupted biphasic insulin release and exhibit insulin resistance in fat and muscle tissue. We found that the absence of NOX4 in C57BL/6J mice affects LO architecture. Wildtype (WT) mice on a normal, predominantly carbohydrate diet (ND) have the majority of small LO with an area of up to 5 000 μm2 (measured on histological sections). High-fat diet (HFD) feeding of WT for 8 weeks leads to the development of diabetic phenotype and...