Modifications d'activité des transporteurs rénaux du glucose : données moléculaires et pharmacologiques

Physiological studies in animals and in humans show that the kidney plays an important role to control the plasma glucose concentration in healthy subjects and in diabetic patients as well. The kidney participates to the gluconeogenesis and controls the amount au glucose reabsorbed in the proximal tubule. Glucose reabsorption requires the coordinate activity of apical and basolateral glucose transporters, SGLT1 and SGLT2, and GLUT1 and GLUT2, respectively. SGLT2 and GLUT2 transporters account for the great majority of glucose reabsorption in the kidney. SGLT2 and GLUT2 expression is increased during diabetes because of the overexpression of transcriptional factors. These modifications contribute to the hyperglycemia. Mutations or invalidation of the renal glucose transporter genes have contributed to understand the function of these transporters. Among the glucose transporters only SGLT2 has an expression restricted to the kidney. Inactivating mutations of the glucose transporters lead to severe phenotype except for SGLT2 mutations. For all these reasons SGLT2 inhibitors have been developed in order to improve the control of plasma glucose concentration in diabetic patients, with the hope of mild side-effects and few interferences with other treatments.