Berghöfer P, Peterson R G, Schneider K, Fehmann H C, Göke B
Clinical Research Unit for Gastrointestinal Endocrinology, Philipps University, Marburg, Germany.
Metabolism. 1997 Mar;46(3):261-7. doi: 10.1016/s0026-0495(97)90251-1.
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 bowel 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.
为了阐明促胰岛素肠道激素葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）的产生是否会因糖尿病代谢状态而改变，对它们在肠道中的表达模式进行了评估。使用了两种糖尿病啮齿动物模型，非肥胖糖尿病（NOD）小鼠作为胰岛素依赖型糖尿病模型，以及Zucker糖尿病脂肪（ZDF）大鼠作为非胰岛素依赖型糖尿病（NIDDM）模型。两种肠促胰岛素激素的表达遵循典型模式，在两种动物中相似且不受糖尿病状态影响。GIP基因在十二指肠、空肠和回肠中大量表达，从肠道上部到下部持续下降。无论糖尿病状态如何，在NOD小鼠和ZDF大鼠中均观察到这种模式。该表达数据通过对基因产物GIP的放射免疫分析（RIA）得到证实。编码GLP-1的胰高血糖素原基因的表达呈现相反的情况。在大肠和回肠中观察到最高表达。对基因产物GLP-1的RIA分析反映了这些数据。尽管两种动物模型中的分布模式相似，但与糖尿病NOD小鼠不同，在糖尿病ZDF大鼠中发现了调节性表达。与瘦的非糖尿病对照相比，肥胖的高血糖动物结肠中胰高血糖素原基因的表达增加，同时小肠中的表达减少。结肠和回肠中的GLP-1含量反映了这一点。总体而言，与瘦的Zucker大鼠（12.4±1.8 pmol）相比，ZDF大鼠的基础GLP-1血浆水平升高（17.0±2.8 pmol）。总之，肠促胰岛素激素（GIP和GLP-1）在整个肠道中遵循特定模式表达，且不受糖尿病状态影响。在ZDF大鼠中，胰高血糖素原表达的调节主要发生在大肠。
