EGCG ‐rich green tea extract stimulates s RAGE secretion to inhibit S 100 A 12‐ RAGE axis through ADAM 10‐mediated ectodomain shedding of extracellular RAGE in type 2 diabetes

The receptor for advanced glycation of end products ( RAGE ) plays a critical role in the progression of type 2 diabetes ( T 2 D ). Soluble RAGE (s RAGE ) is one of the RAGE variants, which acts as a decoy domain receptor and competes with RAGE , thus contributing to prevention of T 2 D . In this study, we conducted clinical trials of (–)‐epigallocatechin‐3‐gallate ( EGCG ) rich green tea extract (300–900 mg/day) to investigate the effect of EGCG on relationship between S 100 A 12 RAGE ligand and diverse s RAGE in T 2 D . Moreover, mechanism of s RAGE production also confirmed in vitro. Our data indicated that EGCG could stimulate s RAGE circulation but inhibited RAGE ligand in T 2 D , and ADAM 10‐mediated ectodomain shedding of extracellular RAGE was mainly involved in EGCG ‐stimulated s RAGE circulation. The present evidence indicates that EGCG has a potential to block S100A12‐ RAGE axis by stimulating s RAGE production through ADAM 10‐mediated ectodomain shedding of extracellular RAGE . Therefore, EGCG contributes to nutritional strategies for diabetes, not only because of its efficient antioxidant activity to scavenge free radicals, but also because of its ability stimulating s RAGE release in the circulation. Additionally, ADAM 10‐induced ectodomain shedding of extracellular RAGE leading to s RAGE circulation should be a potential of passive mechanism of s RAGE production to block S 100 A 12‐ RAGE axis‐related pathogenesis of proinflammation and diabetes.