Dubé Philip E, Forse Catherine L, Bahrami Jasmine, Brubaker Patricia L
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Gastroenterology. 2006 Aug;131(2):589-605. doi: 10.1053/j.gastro.2006.05.055.
BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that acts through unknown pathways to induce intestinal growth. We investigated the role of the insulin-like growth factors (IGF-1 and IGF-2) as mediators of GLP-2-enhanced growth in the murine intestine.
IGF-1 expression and secretion were determined in GLP-2-responsive primary intestinal cultures treated with GLP-2. Parameters of intestinal growth were assessed in wild-type (CD1, Igf1(+/+) and Igf2+), heterozygous (Igf1(+/-)), and null (Igf1(-/-) and Igf2(-P)) mice treated chronically with saline, GLP-2, IGF-1, or R-Spondin1.
GLP-2 increased IGF-1 messenger RNA expression and IGF-1 secretion in intestinal cultures and increased expression of IGF-1 messenger RNA in mouse small intestine in vivo. Igf1(+/+) and Igf2+ mice responded to .1 microg/g(-1) per day(-1) GLP-2 with increased intestinal weights, morphometric parameters, and proliferative indices. In contrast, Igf1(-/-) mice were unresponsive to the same dose of GLP-2, failing to demonstrate changes in intestinal weight, morphometry, or proliferation. However, a significant effect of 1 microg/g(-1) per day(-1) GLP-2 was observed in Igf1(-/-) mice, but only in terms of small intestinal weight when normalized for body weight. Furthermore, Igf2(-P) mice demonstrated a partially impaired response in terms of small intestinal growth. Both Igf1(-/-) and Igf2(-P) mice exhibited normal-enhanced intestinal growth in response to IGF-1 and/or R-Spondin1.
GLP-2 enhances intestinal IGF-1 expression and secretion, and IGF-1 is required for small and large intestinal growth in response to GLP-2. These findings identify IGF-1 as an essential mediator of the intestinotropic actions of GLP-2.
胰高血糖素样肽-2（GLP-2）是一种肠道激素，通过未知途径发挥作用以诱导肠道生长。我们研究了胰岛素样生长因子（IGF-1和IGF-2）作为GLP-2促进小鼠肠道生长的介质所起的作用。
在用GLP-2处理的对GLP-2有反应的原代肠道培养物中测定IGF-1的表达和分泌。对野生型（CD1、Igf1(+/+)和Igf2+）、杂合子（Igf1(+/-)）和纯合缺失（Igf1(-/-)和Igf2(-P)）小鼠长期给予生理盐水、GLP-2、IGF-1或R-Spondin1，评估肠道生长参数。
GLP-2增加了肠道培养物中IGF-1信使核糖核酸的表达和IGF-1的分泌，并在体内增加了小鼠小肠中IGF-1信使核糖核酸的表达。Igf1(+/+)和Igf2+小鼠对每天0.1μg/g(-1)的GLP-响应表现为肠道重量增加、形态学参数改善和增殖指数升高。相比之下，Igf1(-/-)小鼠对相同剂量的GLP-2无反应，未能表现出肠道重量、形态学或增殖方面的变化。然而，在Igf1(-/-)小鼠中观察到每天1μg/g(-1)的GLP-2有显著作用，但仅在按体重标准化后的小肠重量方面。此外，Igf2(-P)小鼠在小肠生长方面表现出部分受损的反应。Igf1(-/-)和Igf2(-P)小鼠对IGF-1和/或R-Spondin1均表现出正常增强的肠道生长。
GLP-2增强肠道IGF-1的表达和分泌，并且IGF-1是GLP-2诱导小肠和大肠生长所必需的。这些发现确定IGF-1是GLP-2促肠作用的重要介质。
