The Entire Small Intestine Mediates the Changes in Glucose Homeostasis After Intestinal Surgery in Goto-Kakizaki Rats
The Entire Small Intestine Mediates the Changes in Glucose Homeostasis After Intestinal Surgery in Goto-Kakizaki Rats
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整个小肠介导后藤柿崎大鼠肠道手术后血糖稳态的变化
DOI：
10.1097/sla.0b013e31826c3866
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发表时间：
2012-12-01
影响因子：
9
通讯作者：
Hu, Sanyuan
中科院分区：
文献类型：
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作者：
Liu, Shaozhuang;Zhang, Guangyong;Hu, Sanyuan
目的：探讨Goto-Kakizaki（GK）大鼠肠道手术后，排除前肠和插入后肠之间的相互作用以及小肠不同部位在调节某些糖调节机制和葡萄糖稳态变化中的作用。背景：先前的研究揭示了在排除前肠和单独插入后肠后，葡萄糖调节机制和葡萄糖稳态的变化，并导致“前肠假说”和“后肠假说”。然而，这些假设并不相互排斥。方法：采用GK大鼠，分别行十二指肠空肠转流术（DJB）、回肠间置术（IT）、回肠间置空肠转流术（DJBIT）、回肠下间置术（sIT）和假手术。主要结果指标为口服葡萄糖耐量（在0、2、4、8和24周进行研究）、胰岛素敏感性、β细胞功能和餐后胰高血糖素样肽-1（GLP-1）、肽YY（PYY）和葡萄糖依赖性促胰岛素肽（GIP）水平（在2周和24周进行评价）。结果：术后2周时对照组体重高于手术组，术后24周时各组体重相似。DJBIT治疗组糖耐量和胰岛素敏感性明显改善（P < 0.05）。广义线性混合模型分析证实，非假手术组的糖耐量随时间推移而改善（P < 0.001），具有显著的时间×治疗交互作用（P < 0.001）。非假手术后空腹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sub-IT组相比，IT组糖耐量显著改善（P < 0.05），餐后胰岛素、GLP-1和PYY水平显著升高（P < 0.05），胰岛素敏感性和空腹C肽水平无显著差异（P > 0.05）。所有手术操作均不影响葡萄糖刺激的GIP水平（P > 0.05）。结论：本研究提供的实验证据表明，排除前肠和插入后肠提供了独立的和协同的变化，葡萄糖稳态GK大鼠肠道手术后，葡萄糖耐量随时间的推移而改善。
Objective: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. Background: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. Methods: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, &bgr;-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). Results: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). Conclusions: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.