Glycated whey proteins protect NOD mice against type 1 diabetes by increasing anti-inflammatory responses and decreasing autoreactivity to self-antigens

Our previous studies suggested that early glycation products (EGPs) generated in the first step of Maillard reaction/glycation were anti-inflammatory. The objectives of the present study were to determine the effects of EGPs derived from the whey protein isolate-glucose system on type 1 diabetes (T1D), and the underlying immunological mechanisms. In non-obese diabetic (NOD) mice, EGPs at the physiological dose of 600 mg/kg/day increased glucose metabolism, decreased non-fasting blood glucose levels and T1D incidence, decreased insulin resistance, and decreased the pancreatic immune infiltration. The protective effects were accompanied with decreases in CD4(-)CD8(+) thymocytes, CD8(+) T cells and serum insulin autoantibody levels, and increases in splenic CD4(+)CD25(+) T cells, macrophage M2/M1 ratio and serum IL-10 level. However, similar treatment with EGPs produced minimal effect on the multiple low-dose streptozotocin-induced hyperglycemia. In conclusion, EGPs protected NOD mice against T1D via increasing anti-inflammatory immune responses and decreasing autoreactivity to self-antigens.