Nauck M A, Siemsglüss J, Orskov C, Holst J J
Department of Medicine, Georg-August-University, Göttingen, Germany.
Z Gastroenterol. 1996 Mar;34(3):159-66.
Glucagon-like peptide 1 (GLP-1[7-36 amide]) is an incretin hormone primarily synthesized in the lower gut (ileum, colon/rectum). Nevertheless, there is an early increment in plasma GLP-1 immediately after ingesting glucose or mixed meals, before nutrients have entered GLP-1 rich intestinal regions. The responsible signalling pathway between the upper and lower gut is not clear. It was the aim of this study to see, whether small intestinal resection or colonectomy changes GLP-1[7-36 amide] release after oral glucose. In eight healthy controls, in seven patients with inactive Crohn's disease (no surgery), in nine patients each after primarily jejunal or ileal small intestinal resections, and in six colonectomized patients not different in age (p = 0.10), body-mass-index (p = 0.24), waist-hip-ratio (p = 0.43), and HbA1c (p = 0.22), oral glucose tolerance tests (75 g) were performed in the fasting state. GLP-1[7-36 amide], insulin C-peptide, GIP and glucagon (specific (RIAs) were measured over 240 min.
Repeated measures ANOVA, t-test (significance: p < 0.05). A clear and early (peak: 15-30 min) GLP-1[7-36 amide] response was observed in all subjects, without any significant difference between gut-resected and control groups (p = 0.95). There were no significant differences in oral glucose tolerance (p = 0.21) or in the suppression of pancreatic glucagon (p = 0.36). Colonectomized patients had a higher insulin (p = 0.011) and C-peptide (p = 0.0023) response in comparison to all other groups. GIP responses also were higher in the colonectomized patients (p = 0.0005). Inactive Crohn's disease and resections of the small intestine as well as proctocolectomy did not change overall GLP-1[7-36 amide] responses and especially not the early increment after oral glucose. This may indicate release of GLP-1[7-36 amide] after oral glucose from the small number of GLP-1[7-36 amide] producing L-cells in the upper gut rather than from the main source in the ileum, colon and rectum. Colonectomized patients are characterized by insulin hypersecretion, which in combination with their normal oral glucose tolerance possibly indicates a reduced insulin sensitivity in this patient group. GIP may play a role in mediating insulin hypersecretion in these patients.
胰高血糖素样肽1（GLP - 1[7 - 36酰胺]）是一种肠促胰岛素激素，主要在肠道下段（回肠、结肠/直肠）合成。然而，在摄入葡萄糖或混合餐食后，在营养物质进入富含GLP - 1的肠道区域之前，血浆GLP - 1会立即出现早期升高。上消化道和下消化道之间的相关信号通路尚不清楚。本研究的目的是观察小肠切除术或结肠切除术是否会改变口服葡萄糖后GLP - 1[7 - 36酰胺]的释放。对8名健康对照者、7名非活动期克罗恩病患者（未接受手术）、9名分别接受了原发性空肠或回肠小肠切除术的患者以及6名年龄无差异（p = 0.10）、体重指数无差异（p = 0.24）、腰臀比无差异（p = 0.43）和糖化血红蛋白无差异（p = 0.22）的结肠切除患者，在空腹状态下进行口服葡萄糖耐量试验（75克）。在240分钟内测量GLP - 1[7 - 36酰胺]、胰岛素C肽、GIP和胰高血糖素（特异性放射免疫分析法）。
重复测量方差分析、t检验（显著性：p < 0.05）。在所有受试者中均观察到明显且早期（峰值：15 - 30分钟）的GLP - 1[7 - 36酰胺]反应，肠道切除组与对照组之间无任何显著差异（p = 0.95）。口服葡萄糖耐量（p = 0.21）或胰腺胰高血糖素的抑制情况（p = 0.36）无显著差异。与所有其他组相比，结肠切除患者的胰岛素（p = 0.011）和C肽（p = 0.0023）反应更高。结肠切除患者的GIP反应也更高（p = 0.0005）。非活动期克罗恩病、小肠切除术以及直肠结肠切除术并未改变总体GLP - 1[7 - 36酰胺]反应，尤其是口服葡萄糖后的早期升高。这可能表明口服葡萄糖后GLP - 1[7 - 36酰胺]是由上消化道中少量产生GLP - 1[7 - 36酰胺]的L细胞释放，而非来自回肠、结肠和直肠的主要来源。结肠切除患者的特征是胰岛素分泌过多，这与他们正常的口服葡萄糖耐量相结合，可能表明该患者组胰岛素敏感性降低。GIP可能在介导这些患者的胰岛素分泌过多中起作用。
