The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice
The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice
复制标题
DOI：
10.1016/j.bbrc.2010.11.077
复制
发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
--
作者：
Ogawa, Eiichi;Hosokawa, Masaya;Inagaki, Nobuya
胃抑制多肽（GIP）在进食时从小肠释放并增加胰腺β细胞的胰岛素分泌。虽然已知GIP受体在小肠中表达，但GIP在小肠中的作用尚未完全了解。本研究旨在阐明GIP对肠道葡萄糖吸收和肠道运动的影响。采用单向灌流法测定大鼠在体小肠对葡萄糖的吸收。[C-14]-葡萄糖掺入体外外翻空肠环中用于评价GIP对钠-葡萄糖共转运蛋白（SGLT）的影响。通过口服非吸收标记物后的肠道传输测量小肠运动。GIP腹腔给药以浓度依赖性方式抑制野生型小鼠的葡萄糖吸收，在50 nmol/kg体重的剂量下显示出最大降低。胰高血糖素样肽-1（GLP-1）受体缺陷小鼠。GIP抑制葡萄糖的吸收，在野生型小鼠。[C-14]-葡萄糖摄取的体外检查显示，100 nM GIP未改变野生型小鼠的SGLT依赖性葡萄糖摄取。腹膜内给予GIP（50 nmol/kg体重）后，野生型和GLP-1受体缺陷小鼠的小肠转运均被抑制至40%。此外，生长抑素受体拮抗剂，环生长抑素，减少GIP对野生型小鼠肠道传输和葡萄糖吸收的抑制作用。这些结果表明，外源性GIP通过生长抑素介导的途径而不是通过GLP-1介导的途径减少肠道运动来抑制肠道葡萄糖吸收。(C)2010年爱思唯尔公司All rights reserved.
Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic beta cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [C-14]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice. GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [C-14]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway. (C) 2010 Elsevier Inc. All rights reserved.