Fig. 8. Working model of AGE-induced MD2-TLR4 activation in diabetes.

Schematic illustration showing the key findings of the study. High levels of glucose generate AGE products in the extracellular environment. AGE products bind directly to MD2 and lead to activation of the immune signaling complex MD2-TLR4. Intracellular adaptor proteins such as myeloid differentiation primary response protein-88 (MyD88) are recruited to AGE-MD2-TLR4 complex. TLR4 then leads to activation of mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, and regulation of genes involved in inflammatory and tissue remodeling responses.