title: Sodium glucose cotransporter 2 inhibition in the diabetic kidney: an update.
abstract: OBJECTIVE
  The sodium glucose cotransporter 2 (SGLT2) reabsorbs most of the glucose filtered by the kidneys. SGLT2 inhibitors reduce glucose reabsorption, thereby lowering blood glucose levels, and have been approved as new antihyperglycemic drugs. Although the therapeutic strategy is very promising, many questions remain.
  
  
  RESULTS
  Using validated antibodies, SGLT2 expression was localized to the brush border of the early proximal tubule in the human kidney and was found upregulated in genetic murine models of type 1 and 2 diabetes. SGLT2 may functionally interact with the Na/H exchanger NHE3 in the proximal tubule. SGLT1-mediated reabsorption explains the fractional renal glucose reabsorption of 40-50% during SGLT2 inhibition. SGLT2 is expressed on pancreatic alfa cells where its inhibition induces glucagon secretion. SGLT2 inhibition lowers glomerular filtration rate in hyperfiltering diabetic patients consistent with the tubular hypothesis of diabetic hyperfiltration. New data indicate a potential of SGLT2 inhibition for renal medullary hypoxia and ketoacidosis, but also for blood glucose effect-dependent and independent nephroprotective actions, renal gluconeogenesis inhibition, reduction in cardiovascular mortality, and cancer therapy.
  
  
  CONCLUSIONS
  The findings expand and refine our understanding of SGLT2 and its inhibition, have relevance for clinical practice, and will help interpret ongoing clinical trials on the long-term safety and cardiovascular effects of SGLT2 inhibitors.
authors.affiliation: aDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla bVeterans Affairs San Diego Healthcare System, San Diego cDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Novikov
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000401:mortality; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D005919:Glomerular Filtration Rate; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000502:physiology; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001786:Blood Glucose; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose