Vuguin Patricia M, Kedees Mamdouh H, Cui Lingguang, Guz Yelena, Gelling Richard W, Nejathaim Morris, Charron Maureen J, Teitelman Gladys
Division of Pediatric Endocrinology, Children's Hospital at Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10476, USA.
Endocrinology. 2006 Sep;147(9):3995-4006. doi: 10.1210/en.2005-1410. Epub 2006 Apr 20.
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.
尽管胰高血糖素（GLU）在葡萄糖稳态中起关键作用，但其在胎儿生长和成熟调节中的作用却知之甚少。在一系列全身性缺失胰高血糖素受体（Gcgr-/-）的小鼠中对这些问题进行了研究，这些小鼠的特征是血糖水平较低，且成年后α细胞和δ细胞增生。Gcgr的缺失对胎儿存活有害；它延迟了β细胞分化，并扰乱了胚胎胰岛中β细胞与α细胞的比例。在成年小鼠中，该突变抑制了α细胞向成熟的进程，影响了几个β细胞特异性基因的表达，并导致α细胞、β细胞和δ细胞数量增加。这种增加是由于胰岛数量的增加以及表达GLU或胰岛素的细胞增殖速率的提高。这些发现表明，GLU参与了一个反馈回路，该回路调节胰岛中不同内分泌细胞类型的比例、每个胰腺中的胰岛数量以及成熟α细胞表型的发育。
