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  • Title: Adiponectin prevents islet ischemia-reperfusion injury through the COX2-TNFα-NF-κB-dependent signal transduction pathway in mice.
    Author: Du X, He S, Jiang Y, Wei L, Hu W.
    Journal: J Endocrinol; 2013 Jul; 218(1):75-84. PubMed ID: 23589741.
    Abstract:
    Islets are exceptionally susceptible to ischemia-reperfusion injury, an increased incidence of primary graft nonfunctionality, and β-cell death during a transplant procedure. Therefore, islets require protection during the early stages of the transplant procedure. Based on the beneficial vascular and anti-inflammatory activity of adiponectin, we hypothesize that adiponectin protects islet cells against ischemia-reperfusion injury and graft dysfunction after transplantation. To examine the effects of adiponectin on the resistance of islet ischemia-reperfusion injury, we used the islet hypoxia-reoxygenation injury model and performed kidney subcapsular syngeneic islet transplants to assess the islets' vitality and function. Furthermore, we utilized lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced damage to islet cells to model the inflammation of post-transplant ischemia-reperfusion injury and transplanted islets in adiponectin knockout mice to explore whether the protective action of adiponectin is involved in TNFα production and nuclear transcription factor-κB (NF-κB) activation. Adiponectin suppressed TNFα production and IκB-α phosphorylation; decreased hypoxia-reoxygenation and LPS-induced and TNFα-induced islet apoptosis; and improved islet function in vivo and in vitro. Our results demonstrate that adiponectin protects the islet from injury. We show that islet protection occurs in response to ischemia-reperfusion and is dependent on the suppression of islet production by TNFα through cyclooxygenase 2 and the inhibition of the TNFα-induced NF-κB activation pathways.
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