Biology Of Sodium‐Absorbing Epithelial Cells: Dawning of a New Era

Schultz, Stanley G.; Hudson, Randall L.

doi:10.1002/cphy.cp060402

Cited by 11 publications

(13 citation statements)

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“…Figure 5 shows the net flows during the short-term increase in mucosal glucose. Focusing on the steady state before and after the step in mucosal glucose, we see that Na ϩ and Cl Ϫ are absorbed from the intestine, in keeping with enterocytes being Na ϩ absorbing epithelia (73). There is a small leak of K ϩ in the opposite direction, which is expected because some of the K ϩ pumped into the cell at the basolateral membrane will escape through K conductance in the apical membrane (Fig.…”

Section: Short-term Response To Mucosal Glucosementioning

confidence: 68%

“…Regulation of basolateral K permeability and potassium homeostasis. The pump-leak parallelism between K permeability and the stimulation of basolateral Na-K-ATPase is well studied (7,28,73). An increase in the Na-K-ATPase pump rate, as seen under the uptake of nutrients, is accompanied by an increase in the basolateral K permeability.…”

Section: Extending the Model To Test Regulatory Mechanismsmentioning

confidence: 99%

“…This requires that the enterocyte possesses intracellular regulatory mechanisms that adjust the compensatory ionic flows to maintain homeostasis. It is known that the inflow of sodium through uptake of glucose and amino acids leads to an increased Na-K-ATPase pump activity (72,73) and a corresponding increase in basolateral K permeability (7,22,28). We will test the hypothesis that these responses, which enable homeostasis of intracellular Na ϩ and K ϩ , are achieved by a direct regulation of Na-K-ATPase production by intracellular Na ϩ together with a regulation of the basolateral permeability for K ϩ based on the Na-K-ATPase pump rate.…”

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confidence: 99%

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Thorsen

Drengstig

Ruoff

2014

American Journal of Physiology-Cell Physiology

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Thorsen K, Drengstig T, Ruoff P. Transepithelial glucose transport and Na ϩ /K ϩ homeostasis in enterocytes: an integrative model. Am J Physiol Cell Physiol 307: C320 -C337, 2014. First published June 4, 2014; doi:10.1152/ajpcell.00068.2013.-The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na ϩ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na ϩ /K ϩ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis.enterocytes; epithelial transport; homeostasis; mathematical modeling; ionic regulation THE UPTAKE AND TRANSPORT OF glucose by the epithelial enterocytes in the small intestine are essential steps in all higher animals. Much of the glucose uptake in the small intestine is coupled to transport of sodium, and the different transporter proteins involved in the sodium coupled glucose uptake are well known (23,61,67,97). Although the electrochemical kinetics of the individual transporter proteins responsible for glucose and nutrient uptake are fairly elucidated (19,54,67,82,97), the combined function in which these transporters drive a net inflow of nutrients from the intestinal lumen to the serosal blood has not yet been modeled in detail.We have developed a mathematical model of an enterocyte that incorporates the available kinetic data from studies on individual transporter proteins. The model includes apical SGLT1 (the glucose sodium cotransporter), coupled apical flow of Na ϩ an...

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Section: Short-term Response To Mucosal Glucosementioning

confidence: 68%

Section: Extending the Model To Test Regulatory Mechanismsmentioning

confidence: 99%

mentioning

confidence: 99%

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Thorsen

Drengstig

Ruoff

2014

American Journal of Physiology-Cell Physiology

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“…In a study of Wild et al (199) , it has been shown that oral polyamine administration may modify the ontogeny of hexose transporter gene expression in the postnatal rat intestine. In this study, the polyamine spermidine, supplied at a level similar to the concentration in rat breast milk (202) , increased the abundance of mRNA for sucrase -isomaltase, SGLT1 and GLUT2, as well as ornithine decarboxylase (ODC) activity and protein and mRNA abundance. The maturational changes in enzyme expression have been correlated to both mucosal polyamine levels and to the onset of the expression and activity of ODC, the key enzyme of polyamine biosynthesis (203) .…”

Section: Bacterial Community and Metabolitesmentioning

confidence: 77%

Intestinal gene expression in pigs: effects of reduced feed intake during weaning and potential impact of dietary components

et al. 2011

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The weaning transition is characterised by morphological, histological and microbial changes, often leading to weaning-associated disorders. These intestinal changes can partly be ascribed to the lack of luminal nutrition arising from the reduced feed intake common in pigs after weaning. It is increasingly becoming clear that changes in the supply with enteral nutrients may have major impacts on intestinal gene expression. Furthermore, the major dietary constituents, i.e. carbohydrates, fatty acids and amino acids, participate in the regulation of intestinal gene expression. However, nutrients may also escape digestion by mammalian enzymes in the upper gastrointestinal tract. These nutrients can be used by the microflora, resulting in the production of bacterial metabolites, for example, SCFA, which may affect intestinal gene expression indirectly. The present review provides an insight on possible effects of reduced feed intake on intestinal gene expression, as it may occur post-weaning. Detailed knowledge on effects of reduced feed intake on intestinal gene expression may help to understand weaning-associated intestinal dysfunctions and diseases. Examples are given of intestinal genes which may be altered in their expression due to supply with specific nutrients. In that way, gene expression could be modulated by dietary means, thereby acting as a potential therapeutic tool. This could be achieved, for example, by influencing genes coding for digestive or absorptive proteins, thus optimising digestive function and metabolism, but also with regard to immune response, or by influencing proliferative processes, thereby enhancing mucosal repair. This would be of special interest when designing a diet to overcome weaning-associated problems.

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“…The membrane transport machinery responsible for electrogenic Na ϩ absorption involves the amiloridesensitive, epithelial-type Na ϩ channel (ENaC) in the apical membrane and the Na ϩ ,K ϩ -ATPase and the K ϩ channel in the basolateral membrane [16]. Thus changes in the activity of any one of these three pathways could contribute to the cAMP-induced regulation of electrogenic Na ϩ absorption.…”

Section: Namentioning

confidence: 99%

The Effect of cAMP on Electrogenic Na+ Absorption in the Rat Distal Colon.

Tsuchiya

Suzuki²

2001

JJP

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Naϩ absorption in the colon plays an important role in salt and water homeostasis. Two transport mechanisms involved in Na ϩ absorption have been described, one being an electroneutral pathway mediated by the apical Na ϩ /H ϩ exchanger, which is functionally coupled to the Cl Ϫ /HCO 3 Ϫ exchanger, and the other an electrogenic pathway (generating the short-circuit current, I sc ) mediated by the apical amiloride-sensitive epithelial-type Na ϩ channel (ENaC) [1]. These two Na ϩ transport pathways are under the control of extracellular neurotransmitters, hormones, and paracrine substances.Cyclic AMP is a ubiquitous second messenger produced in cells in response to extracellular stimulants. cAMP production in the colonic mucosa decreases electroneutral Na ϩ absorption mediated by the NaHowever, previous studies concerning the effect of cAMP on electrogenic Na ϩ absorption in the colon have provided conflicting results. In the intestinal cell line, Caco-2, an I sc component inhibitable by an amiloride analogue, is stimulated by secretin, which acts through the cAMP-signaling pathway [5]. In contrast, cAMP has hardly any effect on 22 Na ϩ absorption in the rabbit colon [6]. In the rat colon, forskolin, an adenylate cyclase activator, has no effect on the amiloride-sensitive I sc under normal conditions, but it can enhance the amiloride-sensitive I sc after the tissue is exposed to sonicated suspensions of nucleated cells [7]. Finally, cAMP and isoproterenol cause, at least initially, a decrease in the amiloride-sensitive I sc in the guinea pig and human colon [8,9].The purpose of this study was therefore to determine the role of cAMP in the regulation of electrogenic Na ϩ absorption in the rat distal colon. To this end we have examined the effect of forskolin and the ␤-adrenergic agonist, isoproterenol, on the amiloridesensitive short-circuit current (I sc ) and unidirectional 22 Na ϩ fluxes in the chamber-mounted rat distal colon from animals pretreated with a low Na ϩ diet to enhance electrogenic Na ϩ absorption. Japanese Journal of Physiology, 51, 435-444, 2001 Key words: cAMP-dependent protein kinase, isoproterenol, ␤-adrenergic agonist, amiloride, Na ϩ absorption. MATERIALS AND METHODS AnimalsAbstract: Cyclic AMP is a ubiquitous second messenger produced in cells in response to extracellular stimulants. The aim of this study was to examine its role in the regulation of amiloridesensitive electrogenic Na ϩ absorption in the rat distal colon by measuring the short-circuit current (I sc ) and 22 Naϩ fluxes in a chamber-mounted mucosal sheet. Forskolin stimulated the amilorideinhibitable I sc and amiloride-inhibitable 22 Na ϩ absorption. 8Br-cAMP also stimulated the amiloride-inhibitable I sc . Furthermore, isoproterenol, acting via ␤-adrenergic activation, stimulated the amiloride-inhibitable I sc . The isoproterenol-induced increase in the amiloride-sensitive I sc was largely suppressed by H89, a protein kinase A inhibitor. In conclusion, cAMP can upregulate amiloride-sensitive electrogenic Na ϩ absorption in ...

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Biology Of Sodium‐Absorbing Epithelial Cells: Dawning of a New Era

Cited by 11 publications

References 290 publications

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Intestinal gene expression in pigs: effects of reduced feed intake during weaning and potential impact of dietary components

The Effect of cAMP on Electrogenic Na+ Absorption in the Rat Distal Colon.

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Biology Of Sodium‐Absorbing Epithelial Cells: Dawning of a New Era

Cited by 11 publications

References 290 publications

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

Intestinal gene expression in pigs: effects of reduced feed intake during weaning and potential impact of dietary components

The Effect of cAMP on Electrogenic Na+ Absorption in the Rat Distal Colon.

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model