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Transepithelial Glucose Transport in the Small Intestine Transepithelial

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Transepithelial Glucose Transport in the Small Intestine Transepithelial REVIEW ARTICLE / PREGLEDNI ČLANAK Transepithelial glucose transport in the small intestine M. Pavić*, M. Šperanda, H. Brzica, S. Milinković-Tur, M. Grčević, I. Prakatur, I. Žura Žaja and M. Ljubojević Abstract The duodenum, jejunum and ileum are SGLT1 transports glucose across the brush parts of the small intestine and the sites of the border membrane, a specific basolateral terminal stages of enzymatic digestion, and membrane glucose transporter, the the majority of nutrient, electrolyte and water sodium-independent glucose transporter absorption. The apical, luminal membrane 2 (GLUT2), transfers glucose out of the of the enterocyte is built of numerous enterocyte down the concentration gradient. microvilli that increase the absorptive The sodium-potassium pump (Na/K- surface of the cell. Carbohydrates, in the ATPase), as a sodium and potassium ion form of monosaccharides, oligosaccharides transporter, is functionally closely related and especially polysaccharides, make up to the sodium-dependent SGLT1. Na/K- the largest quantitative and energetic part of ATPase is responsible for maintaining the the diet of most animals, including humans. electrochemical gradient of sodium ions, as Galactose, fructose and glucose, the final the driving force for glucose transport via degradation products of polysaccharide SGLT1. Transepithelial transport of glucose and oligosaccharide enzymatic digestion, in the small intestine and the differentiation can be absorbed by enterocytes either by of enterocytes occur relatively early during active transport or by facilitated diffusion. the foetal period, allowing glucose to be In the small intestine, the transepithelial absorbed from ingested amniotic fluid. transport of glucose, the most abundant Nutrient transport is possible along the monosaccharide after carbohydrate whole villus-crypt axis during intrauterine digestion and the main source of energy, development, while transport shifts toward is performed by a specific membrane the villus tip in the mature small intestine. transporter located in the brush border With maturation, glucose transport rates membrane of the enterocyte, the sodium- change not only across the villus-crypt axis, glucose cotransporter 1 (SGLT1). While but also along the proximodistal axis in the Mirela PAVIĆ*, DVM, PhD, Assistant Professor, (Corresponding author: e-mail: [email protected]), Suzana MILINKOVIĆ-TUR, DVM, PhD, Full Professor, Ivona ŽURA ŽAJA, DVM, PhD, Assistant Professor, Faculty of Veterinary Medicine, University of Zagreb, Croatia; Marcela ŠPERANDA, DVM, PhD, Full Professor, Manuela GRČEVIĆ, Grad. Food Technol. Eng., PhD, Senior Expert Associate, Ivana PRAKATUR, Grad. Agr. Eng., PhD, Assistant Professor, Faculty of Agrobiotechnical Sciences Osijek, University of Josip Juraj Strossmayer Osijek, Croatia; Hrvoje BRZICA, DVM, PhD, Fidelta Ltd., Zagreb, Croatia; Marija LJUBOJEVIĆ, Grad. Mol. Biol. Eng., PhD, Senior Scientific Associate, Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia VETERINARSKA STANICA 51 (6), 2020. | https://doi.org/10.46419/vs.51.6.1 673 M. PAVIĆ, M. ŠPERANDA, H. BRZICA, S. MILINKOVIĆ-TUR, M. GRČEVIĆ, I. PRAKATUR, I. ŽURA ŽAJA and M. LJUBOJEVIĆ small intestine. The glucose absorption where complex carbohydrates replace less rate shows differences between subunits complex carbohydrates or disaccharides. of the small intestine depending on the Key words: glucose absorption; small age and type of ingested carbohydrates, intestine; SGLT1; GLUT2; Na/K-ATPase Introduction The small intestine (lat. intestinum epithelial cells, enterocytes, arranged in a tenue) of the digestive tract is divided, by single layer, through which the processes length and structure, into three unequal of nutrient absorption in the digestive units: duodenum, jejunum and ileum. tract take place. There are numerous Terminal stages of enzymatic digestion microvilli on the apical, luminal, part are completed and the greatest extent of of the enterocytes, giving the apical cell nutrient, water and electrolyte absorption membrane a brush-like appearance, and take part in the duodenum and proximal therefore, they have been called brush part of the jejunum. Due to its primary border membranes (Caspary, 1992; role, the absorption of nutrients, the Desesso and Jacobson, 2001; Chichlowski small intestine mucosa is highly folded, and Hale, 2008). multiplying its luminal surface several times to increase absorptive capacity. The luminal or absorptive surface of the small Carbohydrate digestion intestine is increased up to 600 times Carbohydrates, in the form of in humans by the presence of valves monosaccharides, oligosaccharides and of Kerckring (~ 3x increase), intestinal especially polysaccharides, account villi (~ 10x increase) and microvilli (~ for more than 50% of the daily caloric 20x increase), compared to the surface intake and thus make up the largest of a simple cylindrical tube of the same quantitative and energetic part of the length. The mucous membrane of the diet of most animals, including humans digestive system, aside being the main (Caspary, 1992). It is thought that people site of absorption, is also the first barrier with a modern dietary pattern, i.e. the for entry of both useful and harmful Western diet, consume about one mole substances into the body, i.e. into the of glucose daily, or approximately 180 blood circulation. The intestinal barrier g glucose, which is absorbed together consists of a single layer of epithelial with approximately 46 g of sodium in the cells with a thin, underlying layer of small intestine (Wright et al., 2007). loose connective tissue (lat. lamina Before being absorbed in the propria) containing lymphatic and blood small intestine, polysaccharides and capillaries. Absorption of nutrients from oligosaccharides need to be broken the lumen of the digestive tract involves down into monosaccharides by digestive transport through the epithelial cell, enzymes. In some species, the enzymatic i.e. transepithelial transport, more than digestion of starch, the most prevalent through the lamina propria and the polysaccharide in the diet of most endothelium, i.e. the wall of the lymphatic domestic animals and humans, already or blood capillaries. The mucosa of the begins in the oral cavity by salivary absorptive part of the digestive tract amylase, then continues in the lumen is made of several types of cells. The of the small intestine by pancreatic most abundant are the highly prismatic amylase and ends on the brush border 674 VETERINARSKA STANICA 51 (6), 673-686, 2020. Transepithelial glucose transport in the small intestine / Prijenos glukoze kroz epitel tankoga crijeva membranes of enterocytes in the small The sodium-potassium pump intestine. The final degradation products of polysaccharides and oligosaccharides (Na/K-ATPase) are monosaccharides – galactose, fructose Although it was previously suggest- and, dominantly, glucose, which can be ed that cellular membranes have trans- absorbed by enterocytes either by active porters for sodium ions, Skou (1957) transport or facilitated diffusion. Glucose was the first to propose the existence of is the main source of energy and an a common sodium and potassium ion important metabolic substrate for protein transporter with energy consumption in and lipid synthesis in mammalian cells. the form of ATP. Transport of sodium The breakdown of glucose in the process ions through the enterocyte takes place of glycolysis and the citric acid cycle either by joint transport with other mole- releases energy in the form of adenosine cules via the sodium-hydrogen exchang- triphosphate (ATP). Glucose is used as a er 3 (NHE3, SLC9A3) through the brush substrate in the synthesis of glycerol to border membrane, or by active transport produce triglycerides and non-essential against the concentration gradient on the fatty acids. Large amounts of glucose basolateral membrane out of the cell via are also used in the mammary gland to Na/K-ATPase (Coon et al., 2011; Rocafull produce lactose during lactation (Wood at al., 2012). and Trayhurn, 2003; Wright et al., 2003; Na/K-ATPase is a highly conserved Zhao and Keating, 2007; Boehlke et al., transmembrane enzyme extremely im- 2015). portant for maintaining cellular home- The tissue glucose amount is largely ostasis. It is responsible for maintaining dependent on the availability, digestion a low intracellular concentration of so- and absorption of carbohydrates in the dium ions and a high concentration of small intestine (Zhao and Keating, 2007). potassium ions, which is important for In addition to absorption from digested maintaining cell membrane potential food, the need for glucose is also and the electrochemical gradient for the enhanced by de novo synthesis of glucose transport of metabolites and nutrients from certain non-carbohydrate carbon across the cell membrane. Na/K-ATPase precursors, i.e. gluconeogenesis, in the is also the only pathway in mammals liver and kidneys. After absorption for transporting sodium ions out of the in the small intestine, a large part of cell under physiological conditions. fructose and almost all galactose are Maintaining cell membrane potential is transformed into glucose in the liver and extremely important in excitable cells, released back into the blood circulation. such as muscle and nerve cells. In addi- It is assumed that 95% of all circulating tion, Na/K-ATPase is also important for monosaccharides are glucose (Guyton maintaining cell volume and osmotic and Hall, 2006).
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