Na+/glucose cotransporter

The effects of D-glucose observed in vivo are not well reproduced in vitro. Madara [203] reported that cytoskeletal contraction and enhanced paracellular permeability were observed only in an in situ perfusion preparation and not in an isolated tissue preparation. Although its in vivo effect was not tested, 25 mM D-glucose, an effective concentration in the jejunum [47], failed to enhance the in vitro transport of sotalol (log PC = -0.62), atenolol (log PC = 0.16), or nadolol (log PC = 0.93) across the isolated conjunctiva [213], For a similar reason and possibly due to the absence of a Na+-glucose cotransporter in the cornea, 25 mM D-glucose was ineffective in increasing the corneal transport of these three drugs. 

K Hosoya, UB Kompella, KJ Kim, VHL Lee. (1996). Contribution of Na+-glucose cotransport to the short-circuit current in the pigmented rabbit conjunctiva. Curr Eye Res 15 447-451. 

Kanai, Y., et al. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J. Clin. Invest. 1994, 93, 397-404. 

Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere. Genomics 1993, 37, 787-789. 

Mackenzie, B., et al. Biophysical characteristics of the pig kidney Na+/ glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2. J. Biol. Chem. 1996, 273, 32678-32683. 

These include energy-consuming pumps (e.g., Na, K-ATPase, p. 130), carriers (e.g for Na/glucose-cotransport, p. 

Turner, J.R. 2000. Show me the pathway Regulation of paracellular permeability by Na+-glucose cotransport. Adv Drug Deliv Rev 41 265. 

The outer membrane, the plasmalemma, efficiently protects the cell from the environment while, at the same time, carrying out functions important for cell metabolism the uptake of substrates and the elimination of toxic compounds. Substrate exchange with the environment is controlled by transport proteins embedded in the membrane (energy-requiring pumps such as Na+,K+-ATPase, or other transport units such as the Na+/glucose cotransporter and sodium and calcium ion channels) [1],... 

Na+-dependent glucose transporters have now been cloned and sequenced from rabbit kidney (Coady et al., 1990), human intestine (Hediger et al., 1989), and LLC-PKi cells (Ohta et al., 1990) and these transporters show 100%, 85%, and 84% identity with the rabbit intestinal carrier (Wright et al., 1992). In addition, Na+-coupled nucleoside (Pajor and Wright, 1992) and amino acid cotransporters (Kong et al., 1993) have been cloned from rabbit kidney and LLC-PKi cells. The amino acid sequence of the cloned nucleoside transporter shows 61% identity and 80% similarity to the Na+-glucose cotransporter sequence. 

A putative Na+-coupled amino acid carrier from LLC-PK cells (A system transporter) (Kong et al., 1993) showed a surprising 76% identity and 89% similarity with the amino acid sequence of the Na+-glucose cotransporter from the same cell line (LLC-PKi cells). Transcripts for this transporter were detected in liver, skeletal muscle, and spleen, tissues that do not express high affinity Na+/glu-cose cotransporter. This putative amino acid transporter has now been identified as a low affinity glucose transporter (Mackenzie et al., 1994). 

Bimir, B., Loo, D.D.F., Wright, E.M. (1991). Voltage clamp studies of the Na+/glucose cotransporter cloned from rabbit small intestine. Eur. J. Physiol. 418,79-85. 

Coady, M.J., Pajor, A.M., Wright, E.M. (1990). Sequence homologies among intestinal and renal Na+/glucose cotransporters. Am. J. Physiol. 259, C605-C610. 

Smith, C.D., Hirayama, B.A., Wright, E.M. (1992a). Baculovirus-mediated expression of the Na+/glucose cotransporter in Sf9 cells. Biochim. Biophys. Acta 1104,151-159. 

Arakawa K, Ishihara T, Oku A et al. (2001) Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095. Br J Pharmacol 132 578-586... 

About 70% of the filtered Na and K is resorbed in the proximal tubule. Sodium is cotransported with glucose and the amino adds, resulting in the resorption of over 99% of these nutrients. Cotransport of Na with bicarbonate results in resorption of 80 to 90% of the filtered bicarbonate. The uptake of these nutrients at the apical membrane occurs by Na mino acid and Na-glucose cotransport systems. One of two sodium ions are cotransported with each glucose. Seven Na-amino acid cotransport systems have been found in the renal tubule. These include systems specific for acidic amino acids, basic amino acids, glycine, neutral amino acids, cysteine, and cystine. One or more sodium ions are cotransported with each amino acid. 

An oral formula suitable for the correction of a variety of diarrheal fluid losses has been recommended by the World Health Organization (WHO). It consists of 90 mM Na, 20 mM K, 80 mM Cl, 30 mM HCO3, and 110 mM glucose. The glucose aids in intestinal absorption of sodium ions, because glucose transport is mediated by the Na-glucose cotransporter. Only low levels of sugar are used in oral replace-... 

The methanol radix extract of Sophora flavescens of a Chinese folklore medicine had potent Na+-glucose cotransporter (SGLT) inhibitory activity. The flavonoids with active SGLT inhibitory activity were kurari-none (13), sophoraflavanone G (10), kushenol K (111), and kushenol N (21) (Fig. 34) [36],... 

Fig. 34 Na+-glucose cotransporter (SGLT) inhibitory flavonoids from radix of Sophora...

Ikumi, Y., Kida, T., Sakuma, S., Yamashita, S. and Akashi, M. (2008) Polymer—phloridzin conjugates as an anti-diabetic drug that inhibits glucose absorption through the Na+ /glucose cotransporter (SGLT1) in the small intestine. Journal of Controlled Release, 125 (1), 42—49. 

Asano, T., Ogihara.T, Katagiii, H, Sakoda, H., Ono, H., Fujishiro, M, Anai, M., Kurihara, H., and Uchijima, Y, (2004) Glucose transporter and Na /glucose cotransporter as molecular targets of anh-diabehc drugs. Current Medicinal Chemistry, 11, 2717-2724. 

Transport of many compounds including drugs across cell membranes is mediated by membrane proteins called carrier proteins or channel proteins. Some of these proteins transport only one substrate molecule at a time across the membrane (uniport systems), while others act as cotransport systems (Figure 9.4). Depending on the direction of the second substrate, the proteins are also called symporters or antiporters, for example, Na /glucose cotransporter, H " /peptide cotransporter, or Na /K antiporter (—Na /K -ATPase). 

Sodium comprises -90% of the cations present in plasma. By contrast, the normal intracellular sodium concentration is generated and controlled by various types of channel proteins such as Na" ", K" "-ATPase and Na -glucose cotransporters inserted into the cell membrane, and these play an important role in the transmission of nerve impulses and translocation of biorelated substances across the cell membrane. The normal sodium ion concentrations in body fluids are listed in Table 1.2-12. 

SLCS Na glucose cotransporter 8 Glucosfamide Glucose-galactose malabsorption syndrome... 

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