Sodium/glucose co-transporter (SGLT) proteins are bound to the cell membrane and have the role of transporting glucose through the membrane into the cells, against the concentration gradient of glucose. This is done by using the sodium gradient, produced by sodium/potassium ATPase pumps, so at the same time glucose is transported into the cells, the sodium is too. Since it is against the gradient, it requires energy to work. SGLT proteins cause the glucose reabsorption from the glomerular filtrate, independent of insulin.
SGLT-2 is a member of the glucose transporter family and is a low-affinity, high-capacity glucose transporter. SGLT-2 is mainly expressed in the S-1 and S-2 segments of the proximal renal tubules where the majority of filtered glucose is absorbed. SGLT-2 has a role in regulation of glucose and is responsible for most glucose reabsorption in the kidneys.
In diabetes, extracellular glucose concentration increases and this high glucose level leads to upregulation of SGLT-2, leading in turn to more absorption of glucose in the kidneys. These effects cause maintenance of hyperglycemia. Because sodium is absorbed at the same time as glucose via SGLT-2, the upregulation of SGLT-2 probably leads to development or maintenance of hypertension. In study where rats were given either ramipril or losartan, levels of SGLT-2 protein and mRNA were significantly reduced. In patients with diabetes, hypertension is a common problem so this may have relevance in this disease.
Drugs that inhibit sodium/glucose cotransporter 2 inhibit renal glucose reabsorption which leads to enhanced urinary glucose excretion and lower glucose in blood. They work independently of insulin and can reduce glucose levels without causing hypoglycemia or weight gain.