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Thorsen K, Drengstig T, Ruoff P. Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model. Am J Physiol Cell Physiol. 2014;307(4):C320-37doi: 10.1152/ajpcell.00068.2013.
Thorsen, K., Drengstig, T., & Ruoff, P. (2014). Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model. American journal of physiology. Cell physiology, 307(4), C320-37. https://doi.org/10.1152/ajpcell.00068.2013
Thorsen, Kristian, et al. "Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model." American journal of physiology. Cell physiology vol. 307,4 (2014): C320-37. doi: https://doi.org/10.1152/ajpcell.00068.2013
Thorsen K, Drengstig T, Ruoff P. Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model. Am J Physiol Cell Physiol. 2014 Aug 15;307(4):C320-37. doi: 10.1152/ajpcell.00068.2013. Epub 2014 Jun 04. PMID: 24898586; PMCID: PMC4137142.
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Am J Physiol Cell Physiol. 2014 Aug 15;307(4):C320-37. doi: 10.1152/ajpcell.00068.2013. Epub 2014 Jun 04.

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

American journal of physiology. Cell physiology

Kristian Thorsen, Tormod Drengstig, Peter Ruoff

Affiliations

  1. Department of Electrical Engineering and Computer Science, University of Stavanger, Stavanger, Norway; and [email protected].
  2. Department of Electrical Engineering and Computer Science, University of Stavanger, Stavanger, Norway; and.
  3. Centre for Organelle Research, University of Stavanger, Stavanger, Norway.

PMID: 24898586 PMCID: PMC4137142 DOI: 10.1152/ajpcell.00068.2013

Abstract

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(+) and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na(+)/K(+) 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.

Copyright © 2014 the American Physiological Society.

Keywords: enterocytes; epithelial transport; homeostasis; ionic regulation; mathematical modeling

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