Department of Surgery, Brigham and Women's Hospital , Boston, Massachusetts.
Harvard Medical School Boston, Massachusetts.
Am J Physiol Gastrointest Liver Physiol. 2018 Feb 1;314(2):G287-G299. doi: 10.1152/ajpgi.00276.2017. Epub 2017 Nov 2.
Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion. Portosystemic gradient was used to calculate intestinal glucose utilization (G), absorption (G), and hormone secretion. Intestinal morphology and gene expression were assessed. At 2 wk, G progressively decreased with increasing BP limb length; this pattern persisted at 4 wk. G increased ≈70% in both RYGB-20cm and -40cm groups at 2 wk. At 4 wk, G progressively increased with limb length. Furthermore, Roux limb weight, and expression of hexokinase and preproglucagon, exhibited a similar progressive increase. At 4 wk, glucagon-like peptide-1 and -2 levels were higher after RYGB-40cm, with associated increased secretion. We conclude that BP limb length modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. Early postoperatively, a longer BP limb reduces G. Later, G, Roux limb hypertrophy, hormone secretion, and hormone levels are increased with longer BP limb. Sustained high incretin levels may prevent weight regain and T2D relapse. These data provide the basis for customizing BP limb length according to patient characteristics and desired metabolic effect. NEW & NOTEWORTHY Biliopancreatic limb length in gastric bypass modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. With a longer biliopancreatic limb, Roux limb hypertrophy, increased glucose utilization, reduced glucose absorption, and sustained high incretin levels may prevent weight regain and diabetes relapse.
尽管 Roux-en-Y 胃旁路手术（RYGB）仍然是治疗肥胖症和 2 型糖尿病（T2D）最有效的方法，但许多患者未能达到缓解或复发。增加 RYGB 的胆胰（BP）支长度可能会改善结果，但这一机制尚不清楚。我们假设 BP 支长度调节 RYGB 的抗糖尿病作用。大鼠接受 20cm（RYGB-20cm）或 40cm（RYGB-40cm）BP 支的 RYGB，并与对照动物进行比较。在 2 和 4 周时，在肠内葡萄糖输注期间采集门静脉和系统血液样本。门脉系统梯度用于计算肠道葡萄糖利用（G）、吸收（G）和激素分泌。评估肠道形态和基因表达。在 2 周时，随着 BP 支长度的增加，G 逐渐降低；这种模式在 4 周时仍然存在。在 RYGB-20cm 和 -40cm 组中，G 在 2 周时均增加了约 70%。在 4 周时，随着支长度的增加，G 逐渐增加。此外，Roux 支重量以及己糖激酶和前胰高血糖素的表达也呈类似的逐渐增加。在 4 周时，RYGB-40cm 后胰高血糖素样肽-1 和 -2 水平升高，同时伴随分泌增加。我们得出结论，BP 支长度调节多种抗糖尿病机制，类似于药物的剂量反应关系。术后早期，较长的 BP 支减少 G。后来，随着 BP 支长度的增加，G、Roux 支肥大、激素分泌和激素水平增加。持续高水平的肠促胰岛素可能防止体重反弹和 T2D 复发。这些数据为根据患者特征和所需代谢效果定制 BP 支长度提供了依据。新的和值得注意的是，胃旁路手术中的胆胰支长度调节多种抗糖尿病机制，类似于药物的剂量反应关系。随着胆胰支的延长，Roux 支肥大、葡萄糖利用率增加、葡萄糖吸收减少以及持续高水平的肠促胰岛素可能防止体重反弹和糖尿病复发。
