The drug octreotide, a somatostatin analog, stimulates the cellular free radical scavenging system and inhibits the release of superoxide anions from monocytes. We hypothesized that octreotide also protects islet β cell function and improves the survival of transplanted islets by ameliorating the adverse effects of hypoxia and reoxygenation on these cells, thus inhibiting apoptosis. To test this hypothesis, we experimentally induced hypoxia in islet cells in mouse insulinoma Min6 cells. Octreotide treatment mildly but significantly improved cell viability under normoxic and hypoxic conditions. Secreted vascular endothelial growth factor (VEGF) from the Min6 cells was downregulated after octreotide treatment during hypoxia. By contrast, the expression of hypoxia-inducible factor (HIF)-1α was upregulated after octreotide treatment under both normoxic and hypoxic conditions. Octreotide treatment also lowered the apoptotic rate of Min6 cells under hypoxic conditions in vitro. In a mouse transplant model, octreotide improved the post-transplantation efficacy and function of islet grafts. Expression of p53 and Bax in islet grafts was upregulated in the recipients treated with octreotide one day after islet transplantation, and the octreotide-treated group produced significantly less Bax than the control group on days 3 and 7 following transplantation. TUNEL assay further demonstrated a decrease in islet cell apoptosis in the octreotide group on days 1, 3, 7, and 14 after transplantation compared with that of the control group (P < 0.05). No islet cell proliferation was found in the octreotide and control groups on days 1, 3, and 7 following transplantation. However, by day 14, the group treated with octreotide demonstrated significantly higher average cell proliferation rates than the controls did (P < 0.05). Thus, octreotide decreased the apoptosis of islets under hypoxic conditions in vitro and enhanced the efficacy of islet transplantation in vivo. Octreotide has excellent potential for therapeutic applications in islet transplantation and merits further study.

中文翻译：

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奥曲肽可减少胰岛细胞凋亡，并提高离体和体内胰岛移植效率。

奥曲肽是一种生长抑素类似物，可刺激细胞自由基清除系统并抑制单核细胞释放超氧阴离子。我们假设奥曲肽还可以通过减轻缺氧和复氧对这些细胞的不利影响来保护胰岛β细胞的功能，并改善移植胰岛的存活率，从而抑制细胞凋亡。为了验证该假设，我们在小鼠胰岛素瘤Min6细胞的胰岛细胞中实验性地诱导了缺氧。在常氧和低氧条件下，奥曲肽治疗可轻度但显着改善细胞活力。在缺氧期间，奥曲肽治疗后，Min6细胞分泌的血管内皮生长因子（VEGF）被下调。相比之下，缺氧诱导因子的表达（HIF）-1 α在常氧和低氧条件下，在奥曲肽治疗后，其上调。在缺氧条件下，奥曲肽处理还降低了Min6细胞的凋亡率。在小鼠移植模型中，奥曲肽改善了胰岛移植物的移植后功效和功能。胰岛移植一天后，接受奥曲肽治疗的受试者的胰岛移植物中p53和Bax的表达上调，奥曲肽治疗组在移植后第3天和第7天产生的Bax明显少于对照组。TUNEL法进一步证实，与对照组相比，奥曲肽组在移植后第1、3、7和14天的胰岛细胞凋亡减少（P <0.05）。移植后第1、3和7天，在奥曲肽和对照组中未发现胰岛细胞增殖。然而，到第14天，用奥曲肽治疗的组的平均细胞增殖率明显高于对照组（P < 0.05）。因此，奥曲肽在体外低氧条件下减少了胰岛的细胞凋亡，并增强了体内胰岛移植的功效。奥曲肽在胰岛移植中具有极好的治疗应用潜力，值得进一步研究。