Journal
JOURNAL OF ENDOCRINOLOGY
Volume 218, Issue 1, Pages 75-84Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-12-0568
Keywords
ischemia-reperfusion; islet transplantation; adiponectin
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Islets are exceptionally susceptible to ischemia-reperfusion injury, an increased incidence of primary graft nonfunctionality, and beta-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 alpha (TNF alpha)-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 TNF alpha production and nuclear transcription factor-kappa B (NF-kappa B) activation. Adiponectin suppressed TNF alpha production and I kappa B-alpha phosphorylation; decreased hypoxia-reoxygenation and LPS-induced and TNF alpha-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 TNF alpha through cyclooxygenase 2 and the inhibition of the TNF alpha-induced NF-kappa B activation pathways.
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