from <0.4 mMin the non-absorptive state to
several mMduring the absorptive state. The
range in concentration will be even more
for luminal glucose concentration, con-
servatively estimated from 0.2 to 50 mM
(Ferraris et al., 1990). Glucose concentra-
tion in the unstirred layer can be estimated
only with uncertainty, and may exceed
several hundred mM(Pappenheimer, 1993).
Measurements of Kms were made for
luminal substrates. Assuming the Kms are
similar on the cytosolic surface, SGLT1
will be loaded with substrate on the
luminal surface and substrates unloaded
on the cytosolic surface. A summary
diagram is provided in Fig. 6.1.
The SGLT1 system for glucose transport
is active, requiring expenditure of ATP. The
events on the apical membrane that bring
glucose into the enterocyte do not involve
direct hydrolysis of ATP. Na+is the primary
solute and is transported down an electro-
chemical gradient requiring no energy. The
secondary solute, glucose, can be carried up
a concentration gradient with no immediate
expenditure of ATP. Energy must be used,
however, to maintain the electrochemical
gradient for Na+. The Na+gradient is main-
tained by the Na+/K+-exchange ATPase
pump on the basolateral membrane of the
enterocytes. Exchange of intracellular Na+
for extracellular K+requires hydrolysis of an
ATP. Inhibition of the exchange pump
quickly stops active absorption of glucose.
A second means for transepithelial
transport of sugars is the GLUT5
transporter protein. GLUT5 catalyses
insulin-independent facilitated diffusion of
monosaccharides across the apical
membrane of enterocytes. Carbohydrate-
facilitated diffusion transporters,
GLUT1–GLUT5, have been reviewed (Baly
and Horuk, 1988; Widdas, 1988; Birnbaum,
1992; Elsas and Longo, 1992; Pessin and
Bell, 1992; Thorens, 1992, 1993; Bird et al.,
1996; Olson and Pessin, 1996). Despite the
name GLUT5, glucose is not transported by
GLUT5. GLUT5 is the major route of
uptake for fructose, and fructose uptake is
not inhibited by the presence of glucose.
The transporter is present on the apical
membrane of enterocytes from approxi-
mately mid-villus to the tip. Other sugars
not actively transported, such as ribose,
mannose, arabinose, glucosamine, N-
acetylglucosamine and xylose, are probably
transported by GLUT5. Galactose shares
SGLT1 with glucose.
Transport of glucose across the baso-
lateral membrane of the enterocyte is an
important component of the paracellular
route of glucose absorption. Thus, baso-
lateral glucose transport will be presented
before discussing paracellular absorption.
GLUT2 is the transporter that catalyses
transport of glucose across the basolateral
membrane. The process is insulin-
independent facilitated diffusion. GLUT2 is
expressed on the basolateral membranes of
mature enterocytes, i.e. from the sides of the
villi to the tip but not at the base or in the
crypts. GLUT2 is characterized by a high Km
and high Vmax. The intestinal GLUT2 dis-
plays slight asymmetry with regard to trans-
port kinetics. The Kmfor glucose efflux is
23 mMglucose, approximately half that of
the Kmof influx (48 mMglucose); favouring
glucose efflux from the enterocyte. Transport
asymmetry is not unique. GLUT1, the
erythrocyte glucose transporter, has a differ-
ence between efflux and influx Kms of
approximately an order of magnitude,
favouring influx. The GLUT2 expressed in
hepatocytes and pancreatic islet cells is sym-
metrical. GLUT2 transports glucose, galac-
tose and fructose, the major sugars absorbed
by a transcellular route. Other absorbed
sugars are probably transported by GLUT2.
Accumulation of solutes of active
transport (Na+, glucose, amino acids)
stimulates paracellular absorption (for
reviews, see Madara, 1988; Pappenheimer,
1993; Ballard et al., 1995; Pappenheimer,
1998). Paracellular transport cannot occur
in the absence of active transport. Thus
active transport provides most of the
driving force for paracellular transport.
What is clear is that during the rapid
absorptive state in vivo, the SGLT1 system
is saturated. The mechanisms for the
connections are not determined fully and
the hypothesis itself is not accepted
universally (Ferraris et al., 1990; Fine et al.,
1993). It appears that absorbed solutes128 R.W. Russell and S.A. Gahr