Mécanisme d'action des inhibiteurs du cotransporteur sodiumglucose de type 2 (SGLT2)

Plasma glucose is freely filtered at the renal glomerular level. In control human, there is a physiological mechanism that allows to reabsorb total glucose at the level of renal proximal tubule, independently of insulin. This reabsorption is controlled by glucosesodium cotransporters (SGLT) expressed at the membrane of epithelial cells. SGLT are proteins which allow glucose transport against a concentration gradient. It is in the S1 segment of proximal tubule that 90% of glucose is reabsorbed by glucose-sodium cotransporter-2 (SGLT2). The remaining 10% are reabsorbed in the S3 segment by glucose-sodium cotransporter-1 (SGLT1). In type 2 diabetics, SGLT2 are overexpressed in renal tubule, thus contributing to the worsening of diabetic hyperglycemia. Specific inhibitors of SGLT2 have been developed to reduce the hyperglycemia of diabetic subjects. This aim of the present review is to describe the mechanisms of glucose reabsorption by the kidney in healthy non-diabetic and diabetic subjects, and the biochemical characteristics of main glucose transporters involved in this process.