Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, 11003, Plaza Fragela s/n., Cadiz, Spain.
Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, 11009, Cadiz, Spain.
Obes Surg. 2022 Dec;32(12):4023-4032. doi: 10.1007/s11695-022-06328-x. Epub 2022 Oct 27.
PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.
We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.
RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.
The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.
Roux-en-Y 胃旁路术（RYGB）后肠重塑和吸收段的适应性在导致 2 型糖尿病（T2DM）改善的病理生理事件中起着重要作用。手术后肠吸收襻的肥大和生长与回肠 L 细胞分泌 GLP-2 有关。餐后肠肽酪氨酸-酪氨酸（PYY）激素的分泌被提出作为 GLP-1 分泌的触发因素。我们的目的是确定 PYY 作为 GLP-2 分泌调节剂的作用，作为 RYGB 后吸收段适应的结果。
我们使用非肥胖性正常血糖的啮齿动物模型。在实验组和对照组中测量循环葡萄糖、胰岛素、PYY 和 GLP-2。我们使用了四个组：空腹对照组、假手术组、RYGB 手术组（RYGB）和 RYGB 手术并用 BIIE0246 治疗组（RYGB+BII）。BIIE0246 是 L 细胞中 NPY2 受体拮抗剂。手术后 12 周分析肠道葡萄糖转运体和 GLP-1 和 PYY 肠道表达和肥大。
RYGB 增加了有或没有 BII 治疗的大鼠的 PYY3-36 血浆水平。RYGB 组观察到高胰岛素反应，但对照组或 RYGB+BII 组没有。BIIE0246 治疗限制了 GLP-2 血浆水平。在吸收肠段，与对照组相比，RYGB 后出现肥大和 SGLT1 和 GLUT1 表达减少。
RYGB 后回肠餐后 PYY 分泌增加。这种增加通过其与 L 细胞上的 Y2 受体结合来介导 GLP-2 释放。该机制在手术后吸收段肥大中起作用。
