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D-glucose and other monosaccharides are hydrophilic substances that cannot easily cross the lipophilic bilayer of the cell membrane. Since carbohydrates are most important for supplying energy to essentially all cell types, specific transport mechanisms have evolved. While vesicle-associated glucose transport has been described only recently,1-4 transporter proteins have been known for years. Such proteins are embedded into the cell membrane and function as hydrophilic pores that allow cellular uptake and release and allow transcellular transport of monosaccharides.

Glucose transporter proteins can be divided into two groups: (1) Sodium-dependent glucose transporters (SGLTs, symporter systems, secondary “active” transporters), which are members of the solute carrier family 5 (SLC5), couple sugar transport to the electrochemical gradient of sodium and hence can transport glucose against its own concentration gradient (eFig. 157.1); and (2) facilitative glucose transporters (GLUTs, uniporter systems, “passive” transporters) are members of the SLC2 family that can transport monosaccharides only along an existing gradient (eFig. 157.2). To date, five congenital defects of monosaccharide transport are known (Fig. 157-1). Their clinical picture is the consequence of tissue-specific expression and substrate specificity of the affected transporter.

eFigure 157.1.

Schematic presentation of transport mediated by a sodium-dependent glucose transporter (SGLT) protein. Energy for this process is provided by the action of the sodium/potassium ATPase located at the basolateral side of the cell membrane exporting three sodium ions for the influx of two potassium ions and thus generating an electrical and a chemical gradient. Transport of glucose (or other monosaccharides) at the apical membrane is coupled to the transport of sodium (for details, see Fig. 157-4). While sodium ions here are transported because of the low concentration and the negative charge within the cell, glucose can be transported against its own gradient. Transport for glucose is therefore termed secondary active.

eFigure 157.2.

Schematic presentation of transport mediated by a facilitative glucose transporter (GLUT) protein. GLUT proteins are embedded into the cell membrane, where they can be found in two conformations, with an open side directed to either the outside or the inside of the cell. Affinity of glucose (or other monosaccharides) to the transporter on both sides can be characterized by specific equilibrium constants. Net transport is possible only in the direction of the lower concentration of the sugar.

Figure 157-1.

Overview of glucose transporters within the human organism. Transport across cell membranes is depicted by arrows, and specific transporters are shown as symbols: rounded symbols are used for sodium-dependent, secondary “active” transporters (SGLTs); angular symbols are used for facilitative, “passive” transporters (GLUTs). Red symbols represent the known defects of SGLT1 (glucose-galactose malabsorption), SGLT2 (familial renal glucosuria), GLUT1 (glucose transporter-1 deficiency), and GLUT2 (Fanconi-Bickel syndrome). GLUT10 ...

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