Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2
Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2
复制标题
DOI：
10.1152/ajpgi.1997.273.6.g1252
复制
发表时间：
1997-12-01
影响因子：
4.5
通讯作者：
Brubaker, PL
中科院分区：
文献类型：
--
作者：
Drucker, DJ;DeForest, L;Brubaker, PL
肠上皮生长的控制是通过小肠和大肠不同细胞间隔内生长因子的相互作用来调节的。有关肠道生长对多种生长因子组合的反应的信息很少。本文研究了抗GLP-2二肽酶类似物人[Gly(2)]GLP-2(h[Gly(2)]GLP-2)、表皮生长因子(EGF)、长[Arg(3)]胰岛素样生长因子I(LR(3)IGF-I)、[Gly(1)]IGF-II和人生长激素(HGH)单独或联合皮下注射对小鼠的肠道营养作用。在所测试的剂量下，h[Gly(2)]GLP-2是增加小肠和大肠重量的最有效药物。与单独使用h[Gly(2)]GLP-2的小鼠相比，接受h[Gly(2)]GLP-2和GH或IGF-I处理的小鼠在小肠生长的组织学参数上表现出更大的增加。同时给予所有五种生长因子可显著增加隐窝和绒毛高度以及小肠和大肠的长度和重量。这些实验的结果确定了肠道营养分子的细胞靶点和相对活性的区域差异，并提出了选择性生长因子组合可能有助于增强体内肠道适应的可能性。
The control of intestinal epithelial growth is regulated by interactions of growth factors in various cellular compartments of the small and large bowel. Little information is available on the intestinal growth response to combinations of growth factors. We studied the intestinotrophic properties of a dipeptidyl peptidase TV resistant glucagon-like peptide 2 (GLP-2) analog, human [Gly(2)]GLP-2 (h[Gly(2)]GLP-2), as well as of epidermal growth factor (EGF), long [Arg(3)]insulin-like growth factor I (LR(3)IGF-I), [Gly(1)]IGF-II, and human growth hormone (hGH), administered by subcutaneous injection alone or in combination in mice. At the doses tested, h[Gly(2)]GLP-2 was the most potent agent for increasing small and large bowel mass. Mice treated with h[Gly(2)]GLP-2 and either GH or IGF-I exhibited greater increases in histological parameters of small intestinal growth than did mice treated with h[Gly(2)]GLP-2 alone. Administration of all five growth factors together induced significant increases in crypt plus villus height and in small and large bowel length and weight. The results of these experiments define regional differences in both the cellular targets and relative activities of intestinotrophic molecules and raise the possibility that selective growth factor combinations may be useful for enhancement of intestinal adaptation in vivo.