title: Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes.
abstract: OBJECTIVE
  To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [TmG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique.
  
  
  METHODS
  Subjects with type 2 diabetes (n=12) and matched healthy subjects (n=12) underwent pancreatic/SHC (plasma glucose range 5.5-30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves.
  
  
  RESULTS
  At baseline, type 2 diabetic subjects had elevated TmG, splay, and threshold compared with controls. Dapagliflozin treatment reduced the TmG and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects.
  
  
  CONCLUSIONS
  The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the TmG and threshold at which glucose is excreted in the urine.
authors.affiliation: Corresponding author: Ralph A. DeFronzo, albarado@uthscsa.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Marcus
authors.initials: M
authors.lastname: Hompesch
authors.forename: Sreeneeranj
authors.initials: S
authors.lastname: Kasichayanula
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.forename: Marc
authors.initials: M
authors.lastname: Pfister
authors.forename: Linda A
authors.initials: LA
authors.lastname: Morrow
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Leslie
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
authors.forename: Agatha
authors.initials: A
authors.lastname: Ching
authors.forename: Frank P
authors.initials: FP
authors.lastname: LaCreta
authors.forename: Steven C
authors.initials: SC
authors.lastname: Griffen
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin; D005947:Glucose