Differential expression of glucagon and glucagon-like peptide 1 receptors in mouse pancreatic alpha and beta cells in two models of alpha cell hyperplasia.
Differential expression of glucagon and glucagon-like peptide 1 receptors in mouse pancreatic alpha and beta cells in two models of alpha cell hyperplasia.
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DOI：
10.1016/j.mce.2009.07.024
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发表时间：
2009-11-13
影响因子：
4.1
通讯作者：
Teitelman G
中科院分区：
文献类型：
--
作者：
Kedees MH;Grigoryan M;Guz Y;Teitelman G
胰岛素和胰升糖素之间的平衡决定了葡萄糖的动态平衡，它们分别由胰腺的β细胞和α细胞产生。循环激素水平部分取决于这两种内分泌细胞的质量。然而，与？细胞不同，调节阿尔法细胞数量的信号的同一性是未知的。胰高血糖素受体(gcgr−/−)全局缺失的小鼠和前激素转换酶2(Pc2)被去除的小鼠，该酶参与将原高血糖素转化为成熟的高血糖素，发生α细胞增生。这些观察结果以及GCGR−/−小鼠表现出高水平循环中的胰高血糖素样肽-1的事实表明，胰高血糖素家族的成员可能直接参与α细胞数量的调节。在这项研究中，我们试图确定阿尔法细胞是否表达GCGR和/或胰升糖素样肽-1(GLP1R)的受体。我们检测了这些受体在GCGR−/−、PC2−/−小鼠和对照仔鼠的胰岛、α细胞系(αTc1/9)和β细胞系(βTC3)中的表达。GCGR仅由胰岛β细胞表达，而不是由α细胞表达，这两个品系的小鼠缺乏胰高血糖素信号。类似地，αTC细胞表达GCGR，但不表达GCGR。α细胞GLP-1R的表达由小鼠的基因和年龄决定。在胚胎中，GCGR+/+小鼠细胞中的GLU+细胞在发育早期表达GLP-1R，但在成年小鼠中不表达。相反，GCGR−/−小鼠的α细胞终生为GLP-1R+，反映了GCGR缺失时GLU+细胞的未成熟状态。与阿尔法细胞不同，所有被检测的小鼠品系的β细胞在出生后启动GLP-1R的表达。这些结果表明，GLP-1可能影响出生后β细胞的成熟，但不影响出生前β细胞的成熟。此外，他们还提示，INTIN可以介导α细胞的增殖，诱导GCGR−/−小鼠α细胞的增殖。
Glucose homeostasis is determined by a balance between insulin and glucagon, produced by beta and alpha cells of the pancreas respectively. The levels of circulating hormones is partly determined by the mass of these two endocrine cell types. However, in contrast to ß cells, the identity of the signals regulating alpha cell number is not known. Mice with a global deletion of the glucagon receptor (Gcgr−/−) and mice with ablation of prohormone convertase 2 (PC2), the enzyme involved in the conversion of proglucagon into mature glucagon, develop alpha cell hyperplasia. These observations and the fact that Gcgr−/− mice exhibit high levels of circulating glucagon-like peptide-1 (GLP-1) suggested that members of the glucagon family of peptides could be directly involved in the regulation of alpha cell number. In this study we sought to determine whether alpha cells express receptors for Gcgr and/or the glucagon-like peptide-1 (GLP1r). We examined the expression of these receptors in islets of Gcgr−/−, PC2−/− mice and control littermates, in an alpha (αTC1/9) and in a beta (βTC3) cell line. Gcgr was expressed exclusively by islet beta cells, but not by alpha cells, of the two lines of mice lacking glucagon signaling. Similarly, ßTC but not αTC cells, expressed Gcgr. The expression of GLP-1r by alpha cells was determined by the genotype and age of the mice. In embryos, GLU+ cells of Gcgr+/+ mice cells express GLP-1r during early development, but not in adults. In contrast, alpha cells of Gcgr−/− mice were GLP-1r+ throughout life, reflecting the immature state of GLU+ cells when Gcgr is deleted. Unlike alpha cells, beta cells of all mice lines examined initiate GLP-1r expression after birth. These results suggest that GLP-1 may affect the maturation of postnatal but not prenatal beta cells. In addition, they also suggest that the incretin could mediate alpha cell proliferation, inducing the development of alpha cell hyperplasia in Gcgr−/− mice.
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影响因子：
4.8
作者：
Lopez-Talavera, JC;Garcia-Ocaña, A;Stewart, AF
通讯作者：
Stewart, AF
DOI：
10.1073/pnas.94.13.6646
发表时间：
1997-06-24
影响因子：
11.1
作者：
Furuta, M;Yano, H;Steiner, DF
通讯作者：
Steiner, DF
影响因子：
7.7
作者：
HAMAGUCHI, K;LEITER, EH
通讯作者：
LEITER, EH
影响因子：
3.5
作者：
Bonner-Weir, S
通讯作者：
Bonner-Weir, S
影响因子：
2.5
作者：
Kedees, Mamdouh H.;Guz, Yelena;Teitelman, Gladys
通讯作者：
Teitelman, Gladys