Islet transplantation is a promising treatment strategy for type 1 diabetes mellitus (T1DM) patients. However, oxidative stress-induced graft failure due to an insufficient revascularization is a major problem of this therapeutic approach. NADPH oxidase (NOX)2 is an important producer of reactive oxygen species (ROS) and several studies have already reported that this enzyme plays a crucial role in the endocrine function and viability of β-cells. Therefore, we hypothesized that targeting islet NOX2 improves the outcome of islet transplantation. To test this, we analyzed the cellular composition and viability of isolated wild-type (WT) and Nox2^−/− islets by immunohistochemistry as well as different viability assays. Ex vivo, the effect of Nox2 deficiency on superoxide production, endocrine function and anti-oxidant protein expression was studied under hypoxic conditions. In vivo, we transplanted WT and Nox2^−/− islets into mouse dorsal skinfold chambers and under the kidney capsule of diabetic mice to assess their revascularization and endocrine function, respectively. We found that the loss of NOX2 does not affect the cellular composition and viability of isolated islets. However, decreased superoxide production, higher glucose-stimulated insulin secretion as well as expression of nuclear factor erythroid 2-related factor (Nrf)2, heme oxygenase (HO)-1 and superoxide dismutase 1 (SOD1) was detected in hypoxic Nox2^−/− islets when compared to WT islets. Moreover, we detected an early revascularization, a higher take rate and restoration of normoglycemia in diabetic mice transplanted with Nox2^−/− islets. These findings indicate that the suppression of NOX2 activity represents a promising therapeutic strategy to improve engraftment and function of isolated islets.

胰岛移植是 1 型糖尿病 (T1DM) 患者一种有前途的治疗策略。然而，由于血运重建不足而导致的氧化应激诱导的移植失败是这种治疗方法的主要问题。NADPH 氧化酶 (NOX)2 是活性氧 (ROS) 的重要产生者，多项研究已报道该酶在 β 细胞的内分泌功能和活力中发挥着至关重要的作用。因此，我们假设靶向胰岛 NOX2 可以改善胰岛移植的结果。为了测试这一点，我们通过免疫组织化学以及不同的活力测定分析了分离的野生型 (WT) 和Nox2 ^{−/−胰岛的细胞组成和活力。}离体研究了缺氧条件下Nox2缺陷对超氧化物产生、内分泌功能和抗氧化蛋白表达的影响。在体内，我们将 WT 和Nox 2 ^−/−胰岛分别移植到小鼠背侧皮褶室和糖尿病小鼠的肾囊下，以分别评估其血运重建和内分泌功能。我们发现 NOX2 的缺失不会影响分离胰岛的细胞组成和活力。然而，在缺氧的Nox2中检测到超氧化物产生减少、葡萄糖刺激的胰岛素分泌增加以及核因子红细胞 2 相关因子 (Nrf)2、血红素加氧酶 (HO)-1 和超氧化物歧化酶 1 (SOD1) 的表达 - ^{/ −}与 WT 胰岛相比的胰岛。此外，我们在移植了Nox2 ^-/−胰岛的糖尿病小鼠中发现了早期血运重建、较高的服用率和正常血糖的恢复。这些发现表明，抑制 NOX2 活性是改善孤立胰岛的植入和功能的一种有前途的治疗策略。