SGLT2 (SODIUM GLUCOSE COTRANSPORTER) - BIOLOGY - 2025

The SGLT2, are proteins belonging to the family of transporters sodium / glucose SGLT. Therefore, they carry out the active transport of the glucose molecule against a concentration gradient. Transport is possible because energy is obtained from sodium cotransport (symport).

In SGLT2, as in all isoforms belonging to the SGLT family, a conformational change is induced in the protein. This is essential to translocate the sugar to the other side of the membrane. This is possible thanks to the current generated by sodium, in addition to the fact that it provides the necessary energy for transport.

The glucose transporter carries out the transport of glucose and sodium against its concentration gradient. By NuFS, San Jose State University, modified of Wikimedia Commons.

This transporter, unlike SGLT1 (sodium-glucose transport proteins), only has the ability to transport glucose. However, the transport kinetics is quite similar in both.

SGLT2 is expressed mainly in the cells of the proximal convoluted tubule of the kidney nephron and its function is to reabsorb the glucose found in the glomerular filtrate that produces urine.

Glucose transport at the cellular level

Glucose is the main sugar through which most cells obtain energy to carry out various metabolic processes.

Because it is a large and highly polar monosaccharide, it cannot by itself cross the cell membrane. That is why to move to the cytosol it requires membrane components called transporter proteins.

The glucose transporters that have been studied and characterized to date carry out the transport of this metabolite by various transport mechanisms.

Said transporter proteins belong to two families: GLUTs (glucose transporters) and SGLTs (sodium / glucose co-transporter family). GLUTs are involved in transporting glucose by facilitated diffusion, while SGLTs carry out monosaccharide transport by active transport.

Structure of SGLT2

According to the analysis of the primary structure of the proteins by means of complementary DNA libraries (cDNA), the transporters of both families present a similar structure.

That is, 12 transmembrane domains in the case of GLUTs and 14 transmembrane domains in SGLTs. Likewise, they all have a glycosylation point on one of the handles oriented towards the extracellular side.

SGLT2 is an integral protein encoded by the SLC5A2 gene and has 672 amino acids with a structure of 14 α-helices. In other words, the secondary structure is quite similar to that of the other members of the SGLT family.

Of the 14 α-helices that make up the three-dimensional structure of the transporter, five of them are spatially arranged in the center of it, with one of the lateral faces of each helix enriched in hydrophobic domains arranged towards the external side in contact with the hydrophobic core of the membrane.

In contrast, the internal face rich in hydrophilic residues is disposed inwards, forming a hydrophilic pore through which the substrates pass.

SGLT2 Features

SGLT2 is a high capacity, low affinity transporter whose expression is limited to the proximal convoluted tubule of the kidney, being responsible for 90% glucose reabsorption.

Glucose transport by SGLT2 is carried out by a symport mechanism, that is, sodium and glucose are transported in the same direction across the membrane against a concentration gradient. The energy stored by the electrochemical gradient is used to carry out the movement of glucose against its gradient.

The inhibition of SGLT2 is associated with a decrease in glucose levels, and with the loss of weight and calories due to the elimination of glucose in the urine.

SGLT2 Features

The function of this transporter is the reabsorption of glucose, it also participates in the reabsorption of sodium and water at the kidney level.

However, the discovery of aquaporins 2 and 6 in the proximal tubule and collecting tubules indicates that a comprehensive investigation should be done on the mechanisms involved in the water and solute transport processes in the tubular epithelium of the kidney.

In addition to participating in the absorption of glucose, GSLT2 participates in the active absorption of water by the kidney. By Henry Vandyke Carter, (https://creativecommons.org/licenses/by-sa/4.0), from Wikimedia Commons.

Renal function and SGLT2

The kidney filters approximately 180 liters of fluid and 160-180 grams of glucose. This filtered glucose is reabsorbed at the level of the proximal tubule, which means that this sugar is absent in the urine.

However, this process is restricted by the renal threshold for glucose. It has been suggested that this transport limit is what allows the maintenance of a necessary glucose supplement when the available concentrations of carbohydrate are low.

This mechanism is affected in diabetic patients because functional alterations occur in the nephron. In this pathology, the increase in glucose concentrations causes a saturation of the transporters, causing glucosuria, especially at the beginning of the disease.

As a result, the kidney undergoes modifications or adaptations that lead to malfunction, among which is an increase in the ability to transport glucose.

The increase in the capacity for glucose transport produces an increase in reabsorption at the level of the renal tubule and the latter is what is related to the overexpression in the number and activity of SGLT2 transporters.

In parallel, the increase in glucose reabsorption occurs with the increase in NaCl reabsorption. The increase in glucose reabsorption, due to the fact that the nephron is working in a forced way, produces an increase in size and an inflammatory state that leads to the development of diabetic nephropathy.

References

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