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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\u2010specific <jats:italic>Cckbr<\/jats:italic> knockout mice and control wild\u2010type 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\u2010SiO<jats:sub>2<\/jats:sub> microspheres (20\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0d<jats:sup>\u22121<\/jats:sup>) are designed so that gastrin specifically stimulates intestinal CCKBR, without its absorption into the circulation. Mice with silenced intestinal <jats:italic>Cckbr<\/jats:italic> has pre\u2010diabetes mellitus (Pre\u2010DM) that rapidly progressed into T2D when fed HFD. Moreover, Gastrin\u2010SiO<jats:sub>2<\/jats:sub> microspheres markedly reduce glucose absorption in duodenum obtained from patients with T2D. In mice with HFD\u2010induced T2D, Gastrin\u2010SiO<jats:sub>2<\/jats:sub> microspheres reduce intestinal glucose absorption by down\u2010regulating intestinal SGLT1 and GLUT2 expressions and stimulating incretin secretion. This study shows the important role of intestinal Gastrin\/CCKBR in intestinal glucose absorption. Gastrin\u2010SiO<jats:sub>2<\/jats:sub> microspheres may be a promising strategy for the treatment of patients with T2D.<\/jats:p>","DOI":"10.1002\/advs.202410032","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T09:42:47Z","timestamp":1739526167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Intestinal Gastrin\/CCKBR Axis Protects against Type 2 Diabetes by Reducing Intestinal Glucose Absorption through the PI3K\/Akt\/eIF4B Signaling Pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Xue","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Laboratory Animal Sciences (CAMS &amp; 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"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Sciences (CAMS &amp; 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