The Impact of Ischemic Stress on the Quality of Isolated Pancreatic Islets

Abstract Background Although the ischemic stress of donated organs has been shown to have strong negative effects on islet recovery, the impact on islet quality remains uncertain. In the present study, therefore, we examined the influence of ischemic stress on the expression of inflammatory mediators among isolated islets. Materials and methods Islets were isolated from adult porcine pancreata subjected to 16-hour cold ischemia time (CIT) in addition to 40-minute warm ischemia time (WIT). We evaluated the islet yield, islet loss during the first 24 hours in culture, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, ATP/DNA ratio, glucose-stimulated respiratory activity, in vivo bioassay, and the expression of inflammatory mediators (tissue factor [TF], [MCP-1], macrophage migration inhibitory factor) on the isolated islets. We also analyzed ATP/DNA ratios of the exocrine tissues during isolation procedures. Results The islet yield, survival rate during culture, and glucose-stimulated respiratory activity were significantly lower in cases of 16-hour CIT plus 40-minute WIT compared with the control group ( P < .0001, .0006, and .002, respectively). In contrast, ADP/ATP ratio as well as TF and MCP-1 expressions on the isolated islets were higher among the ischemic group ( P = .005, .16, and .005, respectively). During isolation procedures, the ATP/DNA of the exocrine tissues was extremely lower in the ischemic compared to the control group ( P < .0001). Notably, however, both ATP/DNA and ADP/ATP ratio of isolated islets were well preserved even in the ischemic group ( P = .45 and .40). Discussion These data suggest that ischemic stress during the preservation period negatively affects the energy status of exocrine tissues. Destruction of the exocrine tissues, in combination with warm ischemic stress during the isolation procedures, subsequently decreases isolated islet activity, inducing the expression of inflammatory mediators.