PHYSIOLOGY AND PATHOLOGY OF RENAL

GLUCOSE TRANSPORT
In the kidney, glucose is freely filtered at the glomerulus and is
reabsorbed via active transport mechanisms in the proximal
convoluted tubule. Two sodium-glucose co-transporters are
responsible for glucose reabsorption: SGLT1 and SGLT2. SGLT1,
which is also found in the gut and other tissues, accounts for about
10% of reabsorption. SGLT2, expressed exclusively in the S1
segment of the proximal tubule, accounts for about 90% of
reabsorption (Figure 1). The concentration gradient that drives the
action of these transporters is driven by the Na+/ATPase pump
and by transport back into the blood via the GLUT2 glucose
transporter (Figure 2). This suggests that the most promising
target for drug development is the SGLT2 transporter, both
because it is responsible for most glucose reabsorption and
because of its exclusive localization to the kidney.

Figure 1. Sites of glucose reabsorption in the S1, S2, and S3

segments of proximal tubules.

Figure 2. Mode of action of SGLT1 and SGLT2.

Further evidence supporting the viability of this approach comes
from studies of people with familial renal glucosuria. This condition
is characterized by variable glucosuria (approx 10-120 g/day), but
is otherwise considered benign, with no known long-term adverse
consequences for health. Benign glucosuria is due to mutations in
the SGLT2 transporter, suggesting that selective pharmacologic
inhibition of SGLT2 is unlikely to have major sequelae other than
induction of glucosuria.