D-Glucose and other monosaccharides are hydrophilic substances that cannot easily cross the lipophilic bilayer of the cell membrane. Since carbohydrates are important for supplying energy to essentially all cell types, specific transport mechanisms have evolved. While vesicle-associated glucose transport has been described fairly recently, 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 transcellular transport of monosaccharides.
Glucose transporter proteins can be divided into 2 groups: (1) sodium-dependent glucose transporters (SGLTs; symporter systems, secondary “active” transporters), which are members of the solute carrier family 5 (SLC5) and couple sugar transport to the electrochemical gradient of sodium, and hence can transport glucose against its own concentration gradient (Fig. 152-1); and (2) facilitative glucose transporters (GLUTs, uniporter systems, “passive” transporters), which are members of the SLC2 family that can transport monosaccharides only along an existing gradient (Fig. 152-2). To date, 5 congenital defects of monosaccharide transport are known (Fig. 152-3). Their clinical picture is the consequence of tissue-specific expression and substrate specificity of the affected transporter.
Schematic 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 3 sodium ions for the influx of 2 potassium ions and thus generating an electrical and chemical gradient. Transport of glucose (or other monosaccharides) at the apical membrane is coupled to the transport of sodium (for details, see Fig. 152-4). 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.
Schematic of transport mediated by a facilitative glucose transporter (GLUT) protein. GLUT proteins are embedded into the cell membrane, where they can be found in 2 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.
Overview of glucose transporters in humans. 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 deficiency (arterial tortuosity syndrome) is not depicted here (see text for more details).