CORM-2 Pretreatment Attenuates Inflammation-mediated Islet Dysfunction

Abstract

During the process of human islet isolation a cascade of stressful events are triggered and negatively influence islet yield, viability, and function, including the production of proinflammatory cytokines and activation of apoptosis. Carbon monoxide-releasing molecule 2 (CORM-2) is a donor of carbon monoxide (CO) and can release CO spontaneously. Accumulating studies suggest that CORM-2 exerts cytoprotective and anti-inflammatory properties. However, the effect of CORM-2 on islet isolation is still unclear. In this study, we found that CORM-2 pretreatment significantly decreased the expression of critical inflammatory genes, including <i>tissue factor</i>, <i>intercellular adhesion molecule-1</i>, <i>chemokine</i> (<i>C-C motif</i>) <i>ligand 2</i>, <i>C-X-C motif chemokine 10</i>, <i>Toll-like receptor 4</i>, <i>interleukin-1β</i>, <i>interleukin-6</i>, and <i>tumor necrosis factor-α</i> (<i>TNF-α</i>). The isolated islets of the CORM-2 pretreatment group showed reduced apoptotic rate, improved viability, and higher glucose-stimulated insulin secretion, and functional gene expression in comparison to control group. Importantly, CORM-2 pretreatment prevented the impairment caused by TNF-α, evidenced by the improved glucose-stimulated index and transplantation outcomes. The present study demonstrated the anti-inflammatory property of CORM-2 during human islet isolation, and we suggest that CORM-2 pretreatment is an appealing treatment to mitigate inflammation-mediated islet dysfunction during isolation and culture ex vivo and to preserve long-term islet survival and function.