2. Academic Validation
  3. Glucose transports in the ileum: mechanism, regulation and physiological role of ileal glucose absorption

Glucose transports in the ileum: mechanism, regulation and physiological role of ileal glucose absorption

  • Biochem Biophys Res Commun. 2025 Oct 20:785:152676. doi: 10.1016/j.bbrc.2025.152676.
Fenglan Chu 1,  Xiongying Chen 2,  Hanxing Wan 3,  Feng Xu 4,  Hui Dong 5
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Qu County People's Hospital, Dazhou City, Sichuan Province, China; Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China. Electronic address: 332651861@qq.com.
  • 2 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China; Department of Pediatrics, Guangyuan Central Hospital, GuangYuan, SiChuan, China.
  • 3 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
  • 4 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China. Electronic address: xufeng9899@163.com.
  • 5 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China. Electronic address: donghui@qdu.edu.cn.
PMID: 41005286 DOI: 10.1016/j.bbrc.2025.152676
Abstract

Glucose-induced electrogenic transport was higher in the distal small intestine compared with the proximal small intestine despite lower glucose transporter expression. We studied the mechanism, regulation and physiological role of ileal glucose absorption using C57BL/6J mice. In Ussing chamber experiments, glucose induced much greater short-circuit current (Isc) in the ileum than in the duodenum and jejunum. 5-HT and activation of adenyl cyclase (AC) attenuated ileal glucose-induced Isc, whereas inhibition of the 5-HT4 receptor (5-HT4R), AC, and PKA potentiated it. Although ileal glucose induced greater Isc in the presence of CA2+, this response was attenuated by inhibiting Na+/H+ exchanger (NHE) and Na+/CA2+ exchanger (NCX). Moreover, stimulation of SGLT1 by glucose and its non-metabolizable analog increased ileal α-defensin 1 (Defa1), α-defensin 5 (Defa5), and lysozyme 1 (Lyz1) mRNA expression. We identified a novel regulatory mechanism governing glucose transport in the ileum, which is activated via NCX or NHE/CA2+ pathway but inhibited via 5-HT4R/cyclic AMP (cAMP)/PKA pathway. Targeting these pathways may help improve intestinal immune defense and also provide a new therapeutic potential in treating glucose absorption disorders.

Keywords

Calcium; Defensins; Glucose; Ileum; SGLT1; cAMP.

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