Rôle des reins dans l’homéostasie du glucose. Implication du cotransporteur sodium–glucose SGLT2 dans le traitement du diabète

Abstract

Kidney plays an important role in glucose homeostasis, both in the post-absorptive and postprandial period. Kidney produces glucose by gluconeogenesis in the renal cortex and uses glucose for covering energy needs of the medulla. Kidney participates also to the reabsorption of filtered glucose in order the terminal urine was devoided of glucose, as long as blood glucose did not exceed 180mg/dL. Reabsorption of glucose is mediated by sodium–glucose cotransporters (SGLT1 et SGLT2) expressed in S1 and S3 segments of proximal tubule. SGLT2 is the main sodium–glucose cotransporter responsible for 90% of glucose reabsorption. In type 2 diabetics, renal gluconeogenesis and glucose utilisation are increased by 30%. Surprisingly, renal glucose reabsorption is increased, participating to worsening of hyperglycemia. This results from the increase in the renal threshhold of glucose reabsorption (220mg/dL) and from an overexpression of SGLT2 in response to hyperglycemia and of cytokine secretion. The administration of SGLT2 inhibitors to type 2 diabetic patients induced a decreased in the renal threshhold of glucose reabsorption (80mg/dL) and strongly reduced kidney glucose reabsorption. The inhibitors of SGLT2 are the only antidiabetic molecules able to correct the excessive renal glucose reabsorption in type 2 diabetics and thus to contribute, by an original mechanism, to the lowering of blood glucose level.