Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation
Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation
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DOI：
10.1210/en.2005-1410
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Teitelman, Gladys
中科院分区：
文献类型：
--
作者：
Vuguin, Patricia M.;Kedees, Mamdouh H.;Teitelman, Gladys
尽管胰高血糖素（GLU）在葡萄糖稳态中发挥着关键作用，但其在调节胎儿生长和成熟中的作用却知之甚少。这些问题在具有GLU受体（Gcgr（-/-））的整体缺失的小鼠系中进行了检查，其特征在于较低的血糖水平以及成人中的α和δ细胞增生。Gcgr的消融对胎儿的存活是有害的;它延迟了β细胞的分化，并扰乱了胚胎胰岛中β细胞与α细胞的比例。在成人中，突变抑制了α细胞成熟的进程，影响了几个β细胞特异性基因的表达，并导致α，β和δ细胞质量的增加。这种增加是由于胰岛数量和表达GLU或胰岛素的细胞增殖速率增加所致。这些发现表明，GLU参与了一个反馈回路，调节胰岛中不同内分泌细胞类型的比例，每个胰腺的胰岛数量以及成熟α细胞表型的发育。
Although glucagon (GLU) plays a pivotal role in glucose homeostasis, its role in the regulation of fetal growth and maturation is poorly understood. These issues were examined in a line of mice with a global deletion of the GLU receptor (Gcgr(-/-)), which are characterized by lower blood glucose levels and by alpha- and delta-cell hyperplasia in adults. Ablation of Gcgr was deleterious to fetal survival; it delayed beta-cell differentiation and perturbed the proportion of beta- to alpha-cells in embryonic islets. In adults, the mutation inhibited the progression of alpha-cells to maturity, affected the expression of several beta-cell-specific genes, and resulted in an augmentation of the alpha-, beta-, and delta-cell mass. This increase was due to an augmentation in both islet number and in the rate of proliferation of cells expressing GLU or insulin. These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype.