Although type 1 diabetes cannot be prevented or reversed, replacement of insulin production by transplantation of the pancreas or pancreatic islets represents a definitive solution. At present, transplantation can restore euglycemia, but this restoration is short-lived, requires islets from multiple donors, and necessitates lifelong immunosuppression. An emerging paradigm in transplantation and autoimmunity indicates that systemic inflammation contributes to tissue injury while disrupting immune tolerance. We identify multiple barriers to successful islet transplantation, each of which either contributes to the inflammatory state or is augmented by it. To optimize islet transplantation for diabetes reversal, we suggest that targeting these interacting barriers and the accompanying inflammation may represent an improved approach to achieve successful clinical islet transplantation by enhancing islet survival, regeneration or neogenesis potential, and tolerance induction. Overall, we consider the proinflammatory effects of important technical, immunological, and metabolic barriers including: 1) islet isolation and transplantation, including selection of implantation site; 2) recurrent autoimmunity, alloimmune rejection, and unique features of the autoimmune-prone immune system; and 3) the deranged metabolism of the islet transplant recipient. Consideration of these themes reveals that each is interrelated to and exacerbated by the other and that this connection is mediated by a systemic inflammatory state. This inflammatory state may form the central barrier to successful islet transplantation. Overall, there remains substantial promise in islet transplantation with several avenues of ongoing promising research. This review focuses on interactions between the technical, immunological, and metabolic barriers that must be overcome to optimize the success of this important therapeutic approach.

中文翻译：

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通过将代谢失调、炎症和免疫调节联系起来解决胰岛移植的难题。

虽然 1 型糖尿病无法预防或逆转，但通过移植胰腺或胰岛来替代胰岛素的产生代表了最终的解决方案。目前，移植可以恢复正常血糖，但这种恢复是短暂的，需要来自多个供体的胰岛，并且需要终生免疫抑制。移植和自身免疫领域的一个新兴范例表明，全身炎症会导致组织损伤，同时破坏免疫耐受。我们确定了成功胰岛移植的多个障碍，每个障碍要么导致炎症状态，要么被它增强。为了优化胰岛移植以逆转糖尿病，我们建议针对这些相互作用的障碍和伴随的炎症可能代表一种改进的方法，通过提高胰岛存活率、再生或新生潜力以及耐受诱导来实现成功的临床胰岛移植。总的来说，我们考虑了重要的技术、免疫和代谢障碍的促炎作用，包括：1) 胰岛分离和移植，包括植入部位的选择；2) 复发性自身免疫、同种免疫排斥和自身免疫倾向免疫系统的独特特征；3）胰岛移植受者代谢紊乱。对这些主题的考虑表明，每一个都相互关联并被另一个加剧，并且这种联系是由全身炎症状态介导的。这种炎症状态可能形成成功胰岛移植的核心障碍。总的来说，胰岛移植仍然有很大的希望，有几种正在进行的有希望的研究。本综述重点关注技术、免疫和代谢障碍之间的相互作用，必须克服这些障碍才能优化这一重要治疗方法的成功。