title: Sodium-glucose cotransport.
abstract: OBJECTIVE
  Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs.
  
  
  RESULTS
  Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways.
  
  
  CONCLUSIONS
  SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2.
authors.affiliation: aInterPrET Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark bVA San Diego Healthcare System, San Diego cDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: Søren Brandt
authors.initials: SB
authors.lastname: Poulsen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fenton
authors.forename: Timo
authors.initials: T
authors.lastname: Rieg
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D051247:Sodium-Glucose Transport Proteins / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; D012964:Sodium; D005947:Glucose