Related Experiment Video

Updated: Apr 29, 2026

Immunostaining to Visualize Murine Enteric Nervous System Development

Immunostaining to Visualize Murine Enteric Nervous System Development

Published on: April 29, 2015

D-glucose acts via sodium/glucose cotransporter 1 to increase NHE3 in mouse jejunal brush border by a Na+/H+ exchange

Rong Lin¹, Rakhilya Murtazina, Boyoung Cha

¹Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Gastroenterology

|October 28, 2010

Abstract

Background & Aims:

Oral rehydration solutions reduce diarrhea-associated mortality. Stimulated sodium absorption by these solutions is mediated by the Na(+)/H(+) hydrogen exchanger NHE3 and is increased by Na(+)-glucose co-transport in vitro, but the mechanisms of this up-regulated process are only partially understood.

Methods:

Intracellular pH was measured in jejunal enterocytes of wild-type mice and mice with disrupted Na+/H+ exchange regulatory co-factor 2 (NHERF2-/- mice) by multiphoton microscopy. Diarrhea was induced by cholera toxin. Caco-2BBe cells that express NHE3 and the sodium/glucose cotransporter 1 (SGLT1) were studied by fluorometry, before and after siRNA-mediated knockdown of NHERF1 or NHERF2. NHE3 distribution was assessed by cell-surface biotinylation and confocal microscopy. Brush-border mobility was determined by fluorescence recovery after photobleaching and confocal microscopy.

Results:

The nonmetabolized SGLT1 substrate α-methyl-D-Glu (α-MD-G) activated jejunal NHE3; this process required Akt and NHERF2. α-MD-G normalized NHE3 activity after cholera toxin-induced diarrhea. α-MD-G-stimulated jejunal NHE3 activity was defective in NHERF2-/- mice and cells with NHERF2 knockdown, but occurred normally with NHERF1 knockdown; was associated with increased NHE3 surface expression in Caco-2 cells, which also was NHERF2-dependent; was associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and was accompanied by a NHERF2 ezrin-radixin-moesin-binding domain-dependent increase in co-precipitation of ezrin with NHE3.

Conclusions:

SGLT1-mediated Na-glucose co-transport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent signaling pathway. It is associated with increased brush-border NHE3 and association between ezrin and NHE3. Activation of NHE3 corrects cholera toxin-induced defects in Na absorption and might contribute to the efficacy of oral rehydration solutions.

More Related Videos

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

Published on: February 3, 2018

Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation

Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation

Published on: December 29, 2023

Related Concept Videos

Secondary Active Transport

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Secondary Active Transport

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Transcellular Transport of Solutes

Transcellular Transport of Solutes

Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...

Glucose Transporters

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

Glucose Absorption Into the Small Intestine

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...

Carbohydrate Absorption

Carbohydrate Absorption

Carbohydrates are essential macronutrients that serve as the body's primary energy source. Their digestion begins in the mouth, where salivary amylase partially breaks down complex carbohydrates such as starch into smaller oligosaccharides. This mechanical and enzymatic activity prepares carbohydrates for further processing in the gastrointestinal tract.
After being swallowed, the partially digested carbohydrates mix with gastric secretions in the stomach. However, the acidic environment...

Articles linked to this work by shared authors, journal, and citation graph.

INSR Armoring Protects CAR-NK and CAR-T Cells Against Tumor Stroma-Induced CAR Shedding by Maintaining Cholesterol Homeostasis.

Cancer research·2026

Dysbiosis-Associated Lysophosphatidic Acid Primes Immune Checkpoint Inhibitor-Induced Intestinal Barrier Dysfunction via the Lysophosphatidic Acid Receptor 2-Myosin Light Chain Kinase Axis.

Cellular and molecular gastroenterology and hepatology·2026

Epithelial MLCK deficiency alleviates alcohol-associated liver disease via dendritic-Th17 cell axis.

JHEP reports : innovation in hepatology·2026

The end of 'leaky gut': pathway-specific mechanistic approaches to barrier restoration.

Current opinion in gastroenterology·2026

Macrophage-derived cathepsin B disrupts intestinal tight junctions through occludin degradation and promotes alcohol-associated liver disease.

Journal of hepatology·2026

Targeting MLCK1 uncouples immune checkpoint inhibitor-induced colitis from antitumour immunity.

Gut·2026

See all related articles