Liu Xue, Liu Xing, Liu Yunpeng, Long Anxiong, Liu Wei, Sun Shiyun, Lu Shuaibing, Wu Xianxian, Jia Xiaodi, Jose Pedro A, Wei Qiang, Jiang Xiaoliang, Zhang Haizeng, Yang Zhiwei
Institute of Laboratory Animal Sciences (CAMS & PUMC), National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, 100021, Beijing, China.
Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, State Key Laboratory of Transvascular Implantation Devices, Heart Regeneration and Repair Key Laboratory Zhejiang Province, 310009, Hangzhou, China.
Adv Sci (Weinh). 2025 Apr;12(13):e2410032. doi: 10.1002/advs.202410032. Epub 2025 Feb 14.
The Gastrin/CCKBR axis is essential for inhibiting intestinal sodium absorption, but its effects on intestinal glucose metabolism remain elusive. This study aims to determine the role of intestinal Gastrin/CCKBR on glucose absorption in the development of type 2 diabetes (T2D). Intestinal epithelial cell-specific Cckbr knockout mice and control wild-type mice are fed normal diet (ND, 10% fat) or high fat diet (HFD, 60% fat) to study the effect of intestinal Gastrin/CCKBR on blood glucose levels. Gastrin-SiO microspheres (20 mg kg d) are designed so that gastrin specifically stimulates intestinal CCKBR, without its absorption into the circulation. Mice with silenced intestinal Cckbr has pre-diabetes mellitus (Pre-DM) that rapidly progressed into T2D when fed HFD. Moreover, Gastrin-SiO microspheres markedly reduce glucose absorption in duodenum obtained from patients with T2D. In mice with HFD-induced T2D, Gastrin-SiO microspheres reduce intestinal glucose absorption by down-regulating intestinal SGLT1 and GLUT2 expressions and stimulating incretin secretion. This study shows the important role of intestinal Gastrin/CCKBR in intestinal glucose absorption. Gastrin-SiO microspheres may be a promising strategy for the treatment of patients with T2D.
胃泌素/CCKBR轴对于抑制肠道钠吸收至关重要，但其对肠道葡萄糖代谢的影响仍不清楚。本研究旨在确定肠道胃泌素/CCKBR在2型糖尿病（T2D）发生发展过程中对葡萄糖吸收的作用。给肠道上皮细胞特异性Cckbr基因敲除小鼠和对照野生型小鼠喂食正常饮食（ND，10%脂肪）或高脂肪饮食（HFD，60%脂肪），以研究肠道胃泌素/CCKBR对血糖水平的影响。设计胃泌素-二氧化硅微球（20mg·kg·d），使胃泌素特异性刺激肠道CCKBR，而不被吸收进入循环。肠道Cckbr基因沉默的小鼠患有糖尿病前期（Pre-DM），喂食HFD后会迅速发展为T2D。此外，胃泌素-二氧化硅微球显著降低T2D患者十二指肠的葡萄糖吸收。在HFD诱导的T2D小鼠中，胃泌素-二氧化硅微球通过下调肠道SGLT1和GLUT2表达以及刺激肠促胰岛素分泌来减少肠道葡萄糖吸收。本研究表明肠道胃泌素/CCKBR在肠道葡萄糖吸收中起重要作用。胃泌素-二氧化硅微球可能是治疗T2D患者的一种有前景的策略。
Zotero 插件
