Familial renal glycosuria and modifications of glucose renal excretion.

Abstract

Under physiological conditions, the kidneys contribute to glucose homoeostasis by producing glucose by gluconeogenesis and preventing glucose loss in urine. The glucose filtered by the glomeruli is completely reabsorbed in the renal proximal tubule. Renal gluconeogenesis produces 25% of the circulating glucose in the postabsorptive state, while the amount of glucose reabsorbed by the kidneys largely exceeds the quantity synthesized by kidney gluconeogenesis. Sodium-glucose cotransporter type 2 (SGLT-2) and glucose transporter 2 (GLUT2) carry out more than 90% of renal glucose uptake. In diabetes, both gluconeogenesis and renal glucose reabsorption are increased. The augmentation of glucose uptake in diabetes is due to the overexpression of renal glucose transporters SGLT-2 and GLUT2 in response to the increase in expression of transcription activator hepatic nuclear factor 1-alpha (HNF1α). The rise in glucose uptake contributes to hyperglycaemia and induces glomerular hyperfiltration by increasing sodium and water reabsorption in the proximal tubule that, in turn, modifies urine flux at the macula densa. SGLT-2 inhibitors improve glycaemic control and prevent renal hyperfiltration in diabetes. Loss of SGLT-2 transporter function is a benign state characterized by glycosuria. In contrast, mutations of other glucose transporters expressed in the kidney are responsible for severe disorders.

• Authors: D Prié
• Journal: Diabetes & metabolism (Diabetes Metab) Vol. 40 Issue 6 Suppl 1 Pg. S12-6 (Dec 2014) ISSN: 1878-1780 [Electronic] France
• PMID: 25554066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Blood Glucose
• Glucose Transporter Type 2
• Hypoglycemic Agents
• Membrane Transport Modulators
• SLC2A2 protein, human
• SLC5A2 protein, human
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors

Topics

• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus (drug therapy, metabolism)
• Glucose Transporter Type 2 (genetics, metabolism)
• Glycosuria, Renal (blood, genetics, metabolism, urine)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Kidney Glomerulus (drug effects, metabolism)
• Kidney Tubules (drug effects, metabolism)
• Membrane Transport Modulators (therapeutic use)
• Models, Biological
• Mutation
• Renal Elimination (drug effects)
• Sodium-Glucose Transporter 2 (genetics, metabolism)
• Sodium-Glucose Transporter 2 Inhibitors
• Up-Regulation