Incretin hormone expression in the gut of diabetic mice and rats
Incretin hormone expression in the gut of diabetic mice and rats
复制标题
DOI：
10.1016/s0026-0495(97)90251-1
复制
发表时间：
1997-03-01
影响因子：
9.8
通讯作者：
Goke, B
中科院分区：
文献类型：
--
作者：
Berghofer, P;Peterson, RG;Goke, B
为了阐明促胰岛素胃肠激素葡萄糖依赖促胰岛素多肽(GIP)和胰升糖素样肽-1(GLP-1)的产生是否会因糖尿病代谢状态而改变的问题，我们评估了它们在肠道中的表达模式。采用非肥胖糖尿病(NOD)小鼠作为胰岛素依赖型糖尿病模型，Zucker糖尿病肥胖(ZDF)大鼠作为非胰岛素依赖型糖尿病(NIDDM)大鼠模型。GIP基因在十二指肠、空肠和回肠中的表达水平较高，从上到下呈递减趋势。在NOD小鼠和ZDF大鼠中都观察到了这种模式，与糖尿病状态无关。基因产物GIP的放射免疫分析(RIA)证实了这一表达数据。而编码GLP-1的胰高血糖素原基因的表达则相反。在大肠和回肠中表达最强。对基因产物GLP-1的RIA分析反映了这些数据。尽管在两种动物模型中分布模式相似，但与糖尿病NOD小鼠相比，糖尿病ZDF大鼠发现了受调控的表达。与瘦削的非糖尿病对照组相比，脂肪高血糖动物的结肠和回肠中GLP-1的含量反映了原胰升糖素基因在结肠中的表达增加和在小肠中的表达减少。总体而言，ZDF大鼠基础血浆GLP-1水平(17.0+/-2.8pmol)高于瘦Zucker大鼠(12.4+/-1.8pmol)。总而言之，胰岛素激素的表达(GIP和GLP-1)在整个肠道中遵循特定的模式，不受糖尿病状态的影响。在ZDF大鼠中，胰高血糖素原表达的调节主要发生在大肠。版权所有(C)1997，由W.B.Saunders公司提供。
To elucidate the question of whether production of the insulinotropic gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) is altered by a diabetic metabolic state, their intestinal expression pattern was evaluated. Two rodent models for diabetes mellitus were used, non-obese diabetic (NOD) mice as a model for insulin-dependent diabetes and Zucker diabetic fatty (ZDF) rats for non-insulin-dependent diabetes mellitus (NIDDM). Expression of both incretin hormones followed typical patterns, which were similar in both animals and unaltered by the diabetic state, The GIP gene was greatly expressed in the duodenum, jejunum, and ileum, with a continuous decrease from the upper to lower intestines. This pattern was observed in both NOD mice and ZDF rats regardless of the diabetic state. This expression data was corroborated by radioimmunoassay (RIA) analysis of the gene product GIP. Expression of the proglucagon gene encoding GLP-1 had an opposite appearance. The highest expression was seen in the large bower and the ileum. RIA analysis of the gene product GLP-1 mirrored these data. Although the distribution pattern was similar in both animal models, in contrast to diabetic NOD mice, a regulated expression was found in diabetic ZDF rats. Compared with lean nondiabetic controls, fatty hyperglycemic animals showed an increased expression of the proglucagon gene in the colon and a concomitant reduction in the small intestine, This was mirrored by the GLP-1 content of the colon and ileum. Overall, basal GLP-1 plasma levels were increased in ZDF rats (17.0 +/- 2.8 pmol) compared with lean Zucker rats (12.4 +/- 1.8 pmol). In conclusion, incretin hormone expression (GIP and GLP-1) follows specific patterns throughout the gut and is unaltered by the diabetic state. In ZDF rats, regulation of proglucagon expression occurs mainly in the large intestine. Copyright (C) 1997 by W.B. Saunders Company.