Dr. Fonseca: What is the role of sodium glucose cotransporters, or SGLTs, in maintaining glucose homeostasis? And how does this role differ in patients with type 2 diabetes?
SGLTs are important in maintaining the balance of glucose. They are responsible for carrying glucose in the gut from the lumen of the gut into the cells and then into the blood. Very little glucose is excreted, because in the [proximal renal] tubule all this glucose is reabsorbed through transporters. This is a two-step process: The SGLTs absorb the glucose from the urine into the tubular cells, and then another transporter transports it into the blood.1-4
There are two important SGLTs in the kidney. One is the SGLT1, and the SGLT2 is probably more important [in the kidney], and is responsible for reabsorption of approximately 90% of the filtered glucose in the urine that reaches the proximal tubule.3-5 If these transporters are not functioning well, then glucose will be excreted in the urine.6 This is seen in patients with renal glycosuria, where other homeostatic mechanisms maintain a normal blood glucose.
There is a threshold above which these transporters are saturated and you reach a maximum reabsorptive capacity. This is usually considered to be around 180 mg/dL of blood glucose—and above that level, the renal threshold, it is no longer possible to reabsorb the large amount of glucose in the urine, and therefore you get glycosuria, and this occurs in diabetes.6,7
Since the transporter SGLT2 has such a major role in reabsorbing glucose in the renal tubule, inhibiting its action would lead to a lack of reabsorption, and therefore increase the glucose excretion in the urine. That can be exploited by using drugs that can block SGLT2 and increase glucosuria.