Impact of whole body irradiation and vascular endothelial growth factor-A on increased beta cell mass after bone marrow transplantation in a mouse model of diabetes induced by streptozotocin
Impact of whole body irradiation and vascular endothelial growth factor-A on increased beta cell mass after bone marrow transplantation in a mouse model of diabetes induced by streptozotocin
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DOI：
10.1007/s00125-008-1172-z
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发表时间：
2009-01-01
期刊：
影响因子：
8.2
通讯作者：
Watada, H.
中科院分区：
文献类型：
--
作者：
Nakayama, S.;Uchida, T.;Watada, H.
目的/假设最近的研究表明，骨髓移植可降低链脲佐菌素诱导的糖尿病小鼠模型的高血糖症。然而，骨髓移植改善高血糖的关键因素尚未完全阐明。本研究的目的就是寻找这些因素。方法我们研究了全身照射、仅腹部照射或全身除腹部照射然后输注或不输注骨髓细胞的效果。我们还研究了骨髓移植对β细胞特异性血管内皮生长因子A基因（Vegfa）基因敲除小鼠的影响。结果骨髓移植改善了链脲佐菌素诱导的高血糖并部分恢复了胰岛质量。这种变化与胰岛血管化增加有关。在研究的其他方法中，在不输注骨髓细胞的情况下进行全身低剂量照射也改善了血糖水平。在链脲佐菌素治疗的β细胞特异性Vegfa基因敲除小鼠中，表现出胰岛血管化受损，骨髓移植既不能改善高血糖、相对β细胞质量，也不能改善胰岛血管化。结论/解释我们的结果表明，在链脲佐菌素治疗后，全身照射对于恢复β细胞质量是必要的，并且足以恢复β细胞质量，不依赖于骨髓细胞的输注。 β 细胞中产生的血管内皮生长因子 A 对于这种现象也至关重要。
Aims/hypothesis Recent studies have shown that bone marrow transplantation reduces hyperglycaemia in a mouse model of diabetes induced by streptozotocin. However, the essential factors for the improvement of hyperglycaemia by bone marrow transplantation have not been fully elucidated. The aim of this study was to search for such factors.Methods We investigated the effect of irradiation to whole body, to abdomen alone or to whole body excluding abdomen, followed by infusion or no infusion of bone marrow cells. We also investigated the effect of bone marrow transplantation on beta cell-specific vascular endothelial growth factor-A gene ( Vegfa) knockout mice.Results Bone marrow transplantation improved streptozotocin-induced hyperglycaemia and partially restored islet mass. This change was associated with increased islet vascularisation. Among the other methods investigated, low-dose irradiation of the whole body without infusion of bone marrow cells also improved blood glucose level. In streptozotocin-treated beta cell-specific Vegfa knockout mice, which exhibit impaired islet vascularisation, bone marrow transplantation neither improved hyperglycaemia, relative beta cell mass nor islet vascularisation.Conclusion/interpretation Our results indicate that whole body irradiation is essential and sufficient for restoration of beta cell mass after streptozotocin treatment independent of infusion of bone marrow cells. Vascular endothelial growth factor-A produced in beta cells is also essential for this phenomenon.