Hydrogen peroxide is important for the upregulation of VCAM‐1 expression in pancreatic beta cells

Although implication of VCAM‐1 in the rejection of pancreatic islet transplantation has been suggested, so far, little is studied about its detailed mode of action and regulatory mechanism. In this study, we first found that among proinflammatory cytokines, lipopolyssacharide and ROS, ROS is the most potent inducer of VCAM‐1 expression in pancreatic islets. Further investigation for identifying VCAM‐1 expressing cells also shows that ROS elicits much higher expression of VCAM‐1 in pancreatic β‐cells than in α‐and microvascular endothelial cells. Furthermore, with adenovirus‐mediated gene transfer of catalase, we elucidated that H2O2 itself is a key molecule for VCAM‐1 expression in pancreatic islet and β‐cells. Pretreatment of cells with inhibitors further reveals that different from PKC, PLD, and PI3K/Akt, extracellular Ca2+ influx is important for H2O2‐induced VCAM‐1 expression in pancreatic β‐cells, suggesting the existence of novel signaling pathways different from endothelial cells. In summary, these results indicate that H2O2 is important for the upregulation of VCAM‐1 expression via the influx of extracellular Ca2+ in pancreatic β‐cells, suggesting that it may play a key role in leukocytes infiltration to pancreatic β‐cell and ultimately result in β‐cells dysfunction in islet graft rejection.