Upregulation of non-β Cell-derived Vascular Endothelial Growth FactorA Increases Small Clusters of Insulin producing Cells in the Pancreas.
Upregulation of non-β Cell-derived Vascular Endothelial Growth FactorA Increases Small Clusters of Insulin producing Cells in the Pancreas.
复制标题
非 β 细胞来源的血管内皮生长因子 A 的上调会增加胰腺中产生胰岛素的细胞小簇。
DOI：
10.1055/s-0034-1371811
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发表时间：
2014
影响因子：
1.8
通讯作者：
Hashiguchi T.
中科院分区：
文献类型：
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作者：
Takenouchi K;Shrestha B;Yamakuchi M;Yoshinaga M;Arimura N;Kawaguchi H;Nagasato T;Feil R;Kawahara K-I;Sakamoto T;Maruyama I;Hashiguchi T.
胰腺β细胞衍生的血管内皮生长因子A（VEGF-A）有助于正常β细胞功能。因此，我们假设非β细胞来源的VEGF-A可能影响其在成年小鼠中的特性，我们在transgelin的控制下以内脏平滑肌细胞（SMC）主导的方式产生表达人VEGF-A（hVEGF-A）的转基因小鼠（Tagln/SM 22 α）启动子通过三苯氧胺诱导Cre/loxP重组系统的研究SM-CreERT 2/hVEGF小鼠口服接受他莫昔芬，随后在hVEGF-A诱导后4周对其胰腺进行显微镜检查。对胰岛、胰管和单个IPC中的胰岛素产生细胞（IPC）簇的数目进行计数。与SM-CreERT 2（Ki）小鼠相比，SM-CreERT 2/hVEGF小鼠中胰腺中的（100-215 μm2）（1992个计数中的473个对976个计数中的199个，p<0.05），尽管总IPC面积和胰管IPC数量（与外分泌面积成比例）在两组之间相似。虽然在SM-CreERT 2/hVEGF小鼠中观察到的大多数小IPC簇不伴有α和/或δ细胞，但一些IPC簇附着于单个或少数α细胞。与SM-CreERT 2（Ki）小鼠相比，SM-CreERT 2/hVEGF小鼠中STZ诱导的糖尿病状态略有改善，在STZ给药后12周仅有一个显著点。非β细胞来源的VEGF-A的上调可能通过增加小IPC簇的数量来改变胰腺IPC的组成。这些发现提供了关于非β细胞来源的VEGF-A对IPC再生和胰岛素产生的作用的新信息。
Pancreatic β cell-derived vascular endothelial growth factor A (VEGF-A) contributes to normal β cell function. We therefore hypothesized that non-β cell-derived VEGF-A may affect its properties in adult mice.We generated transgenic mice expressing human VEGF-A (hVEGF-A) in a visceral smooth muscle cell (SMC)-dominant manner under the control of the transgelin (Tagln/SM22α) promoterviaa tamoxifen-induced Cre/loxP recombination system (SM-CreERT2/hVEGF mice).SM-CreERT2/hVEGF mice received tamoxifen orally followed by microscopic examination of their pancreas 4 weeks after the hVEGF-A induction. The number of clusters of insulin-producing cells (IPCs) in islets, pancreatic ducts, and individual IPCs were counted.The number of small IPC clusters (100–215 μm2) in the pancreas increased significantly in SM-CreERT2/hVEGF mice compared with SM-CreERT2(Ki) mice (473 out of 1 992 counts vs. 199 out of 976 counts,p<0.05), although total IPC area and the number of pancreatic duct IPCs, in proportion to exocrine area, were similar between the 2 groups. Although most small IPC clusters observed in SM-CreERT2/hVEGF mice were not accompanied by α and/or δ cells, some were attached to a single or a few α cells. An STZ-induced diabetic state in SM-CreERT2/hVEGF mice was slightly ameliorated, with only one point of significance 12 weeks after STZ administration, compared with SM-CreERT2(Ki) mice.Upregulation of non-β cell-derived VEGF-A may alter the composition of pancreatic IPCs by increasing the number of small IPC clusters. These findings provide new information on the role of non-β cell-derived VEGF-A to IPC regeneration and insulin production.