Department of Medicine, Metabolism and Endocrinology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Endocr J. 2010;57(3):185-91. doi: 10.1507/endocrj.k09e-035. Epub 2010 Feb 24.
The islet contains a dense vascular structure of several features. The expression of vascular endothelial growth factor (VEGF)-A in beta cells is indispensable for the formation of this structure. Thus, the beta cell-specific VEGF-A-deficient mouse (RIP-Cre:Vegf(fl/fl)) is useful for studying the role of the islet vasculature on the function of islets and regulation of beta cell mass. Studies using RIP-Cre:Vegf(fl/fl) mice revealed that defects in the normal vascular structure are associated with abnormal insulin secretion and concluded that the islet vascular system is essential for normal insulin secretion into the blood stream. On the other hand, whereas the endothelial cells might be involved in regulation of islet mass and the mouse model of diabetes shows that the number of endothelial cells correlate with the islet mass, RIP-Cre:Vegf(fl/fl) mice show almost normal response of islet expansion in the presence of insulin resistance. However, whereas bone marrow transplantation induces islet expansion in control mice, it does not induce the proper expansion of beta cell mass in RIP-Cre:Vegf(fl/fl) mice. These data indicate that the roles of VEGF-A and islet vasculature in the regulation of beta cell mass depends on the stimulus for the islets.
胰岛包含多种特征的密集血管结构。β细胞中血管内皮生长因子 (VEGF)-A 的表达对于这种结构的形成是必不可少的。因此，胰岛特异性 VEGF-A 缺陷小鼠（RIP-Cre:Vegf(fl/fl)）可用于研究胰岛血管系统对胰岛功能和β细胞质量的调节作用。使用 RIP-Cre:Vegf(fl/fl) 小鼠进行的研究表明，正常血管结构的缺陷与胰岛素分泌异常有关，并得出结论，胰岛血管系统对于正常胰岛素分泌到血液中是必不可少的。另一方面，内皮细胞可能参与胰岛质量的调节，糖尿病小鼠模型表明内皮细胞的数量与胰岛质量相关，而 RIP-Cre:Vegf(fl/fl) 小鼠在存在胰岛素抵抗的情况下几乎表现出正常的胰岛扩张反应。然而，尽管骨髓移植可诱导对照小鼠的胰岛扩张，但它不能诱导 RIP-Cre:Vegf(fl/fl) 小鼠中β细胞质量的适当扩张。这些数据表明，VEGF-A 和胰岛血管系统在β细胞质量调节中的作用取决于胰岛的刺激物。
