Departments of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
Ann Surg. 2012 Dec;256(6):1049-58. doi: 10.1097/SLA.0b013e31826c3866.
To investigate the potential interaction between excluding foregut and interposing hindgut and the role of different portions of the small intestine in mediating changes in some glucoregulatory mechanisms and glucose homeostasis after intestinal surgery in Goto-Kakizaki (GK) rats.
Previous studies have revealed changes in glucoregulatory mechanisms and glucose homeostasis after excluding foregut and interposing hindgut alone and lead to the "foregut hypothesis" and "hindgut hypothesis." However, these hypotheses are not mutually exclusive.
Duodenal-jejunal bypass (DJB), ileal interposition (IT), duodenal-jejunal bypass with ileal interposition (DJBIT), sub-ileal interposition (sIT), and sham operations were performed on GK rats. Main outcome measures were oral glucose tolerance (studied at 0, 2, 4, 8, and 24 weeks), insulin sensitivity, β-cell function, and postprandial levels of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic peptide(GIP) (evaluated at 2 and 24 weeks).
Global body weight in the control group was higher than in the operation groups at postoperative week 2, but it was similar among groups at postoperative week 24. The DJBIT procedure induced synergistic improvement in glucose tolerance and insulin sensitivity (P < 0.05). Generalized linear mixed-model analysis confirmed that glucose tolerance in nonsham operation groups improved over time (P < 0.001), with a significant time × treatment interaction (P < 0.001). Fasting C-peptide, postprandial insulin, GLP-1, and PYY levels increased after nonsham operations (P < 0.05); however, they were not significantly different among the DJBIT, DJB, and IT groups (P > 0.05). Compared with sub-IT, IT induced better glucose tolerance (P < 0.05) and higher postprandial insulin, GLP-1 and PYY levels (P < 0.05), and no significant difference in insulin sensitivity and fasting C-peptide was observed (P > 0.05). None of the surgical procedures affected glucose-stimulated GIP levels (P > 0.05).
This study provides experimental evidence that excluding foregut and interposing hindgut provided independent and synergistic changes in glucose homeostasis after intestinal surgery in GK rats and that glucose tolerance improved over time.
研究单独排除前肠和间置后肠以及小肠不同部位在介导 Goto-Kakizaki（GK）大鼠肠手术后某些糖调节机制和葡萄糖稳态变化中的潜在相互作用。
先前的研究揭示了单独排除前肠和间置后肠后糖调节机制和葡萄糖稳态的变化，并导致了“前肠假说”和“后肠假说”。然而，这些假设并不相互排斥。
在 GK 大鼠上进行十二指肠-空肠旁路（DJB）、回肠间置（IT）、十二指肠-空肠旁路+回肠间置（DJBIT）、亚回肠间置（sIT）和假手术。主要观察指标为口服葡萄糖耐量（分别在 0、2、4、8 和 24 周时进行研究）、胰岛素敏感性、β细胞功能以及餐后胰高血糖素样肽-1（GLP-1）、肽 YY（PYY）和葡萄糖依赖性胰岛素释放肽（GIP）水平（分别在 2 和 24 周时进行评估）。
对照组在术后第 2 周时的总体体重高于手术组，但在术后第 24 周时各组间相似。DJBIT 术式协同改善了葡萄糖耐量和胰岛素敏感性（P < 0.05）。广义线性混合模型分析证实，非假手术组的葡萄糖耐量随时间推移而改善（P < 0.001），且存在显著的时间×治疗相互作用（P < 0.001）。非假手术组的空腹 C 肽、餐后胰岛素、GLP-1 和 PYY 水平升高（P < 0.05）；但 DJBIT、DJB 和 IT 组之间无显著差异（P > 0.05）。与亚 IT 相比，IT 诱导了更好的葡萄糖耐量（P < 0.05）和更高的餐后胰岛素、GLP-1 和 PYY 水平（P < 0.05），而胰岛素敏感性和空腹 C 肽无显著差异（P > 0.05）。手术程序均不影响葡萄糖刺激的 GIP 水平（P > 0.05）。
本研究提供了实验证据，表明在 GK 大鼠的肠手术后，排除前肠和间置后肠提供了独立且协同的葡萄糖稳态变化，并且葡萄糖耐量随时间推移而改善。
