Strader April D, Clausen Trine Ryberg, Goodin Sean Z, Wendt Donna
Department of Physiology, Southern Illinois University School of Medicine, 1135 Lincoln Drive, Carbondale, IL, 62901, USA.
Obes Surg. 2009 Jan;19(1):96-104. doi: 10.1007/s11695-008-9754-x. Epub 2008 Nov 7.
The surgical treatment for obesity promotes massive weight loss and early improvement in co-morbid conditions such as type-2 diabetes. Because surgically mediated glycemic improvements are immediate, the mechanisms involved appear to be weight loss independent. Ileal interposition has been used to gain understanding of the relative role that the lower intestine plays in mediating metabolic improvement. Here, we report that ileal interposition is sufficient for improving glucose tolerance in a low-dose streptozotocin-treated diabetic rat model as well as in normal rats with no effect on body weight.
Male Long-Evans rats were treated with streptozotocin (35 mg/kg) or left untreated and then received sham or ileal interposition. Body weight was measured as well as glucose and insulin tolerance. Plasma insulin and gut hormones were measured during the glucose tolerance test.
Streptozotocin treatment resulted in hyperglycemia within 48 h after treatment. Diabetic rats with ileal interposition showed improvement in glucose tolerance as early as 4 weeks after surgery compared to sham (p < 0.05). By 11 weeks after surgery glucose and insulin tolerance was markedly improved in interposed-diabetic compared to sham-diabetic rats (p < 0.05). Normal non-diabetic rats showed improved glucose tolerance after ileal interposition compared to sham (p < 0.05). Insulin secretion was increased in interposed rats following glucose administration (p < 0.05). The ileal-derived hormones glucagon like peptide-1 (GLP-1), peptide YY (PYY), and glucagon were all significantly elevated in the ileal interposed rats (p < 0.01). Gastric inhibitory polypeptide (GIP) was unchanged. In neither study did body weight between the surgical groups differ at any time point.
Ileal interposition effectively improves glucose tolerance in streptozotocin-diabetic and euglycemic rats. Enhanced insulin secretion can explain the lowered glucose concentrations in euglycemic rats following ileal interposition. Ileal interposition is associated with dramatically elevated ileal hormones, GLP-1, PYY, and glucagon (p < 0.01) with no change in the duodenal hormone GIP.
肥胖症的外科治疗可促使体重大幅下降，并使2型糖尿病等合并症得到早期改善。由于手术介导的血糖改善是即时的，其涉及的机制似乎与体重减轻无关。回肠置术已被用于了解下肠道在介导代谢改善中所起的相对作用。在此，我们报告回肠置术足以改善低剂量链脲佐菌素处理的糖尿病大鼠模型以及正常大鼠的葡萄糖耐量，且对体重无影响。
雄性Long-Evans大鼠接受链脲佐菌素（35 mg/kg）处理或不处理，然后接受假手术或回肠置术。测量体重以及葡萄糖和胰岛素耐量。在葡萄糖耐量试验期间测量血浆胰岛素和肠道激素。
链脲佐菌素处理在处理后48小时内导致高血糖。与假手术组相比，接受回肠置术的糖尿病大鼠在术后4周时葡萄糖耐量就有所改善（p < 0.05）。到术后11周时，与假手术糖尿病大鼠相比，接受回肠置术的糖尿病大鼠的葡萄糖和胰岛素耐量明显改善（p < 0.05）。与假手术组相比，正常非糖尿病大鼠在回肠置术后葡萄糖耐量得到改善（p < 0.05）。给予葡萄糖后，接受回肠置术的大鼠胰岛素分泌增加（p < 0.05）。在接受回肠置术的大鼠中，源自回肠的激素胰高血糖素样肽-1（GLP-1）、肽YY（PYY）和胰高血糖素均显著升高（p < 0.01）。胃抑制多肽（GIP）未发生变化。在两项研究中，手术组之间的体重在任何时间点均无差异。
回肠置术可有效改善链脲佐菌素诱导的糖尿病大鼠和血糖正常大鼠的葡萄糖耐量。胰岛素分泌增加可以解释回肠置术后血糖正常大鼠血糖浓度降低的原因。回肠置术与回肠激素GLP-1、PYY和胰高血糖素显著升高相关（p < 0.01），而十二指肠激素GIP无变化。
