Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2

Diabetologia. 2018 Oct;61(10):2087-2097. doi: 10.1007/s00125-018-4656-5. Epub 2018 Aug 22.


The concentration of glucose in plasma is held within narrow limits (4-10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane. 'Knockout' of these transporters in mice and men results in the excretion of filtered glucose in the urine. In humans, intravenous injection of the plant glucoside phlorizin also results in excretion of the full filtered glucose load. This outcome and the finding that, in an animal model, phlorizin reversed the symptoms of diabetes, has stimulated the development and successful introduction of SGLT2 inhibitors, gliflozins, in the treatment of type 2 diabetes mellitus. Here we summarise the current state of our knowledge about the physiology of renal glucose handling and provide background to the development of SGLT2 inhibitors for type 2 diabetes treatment.

Keywords: GLUTs; Gliflozins; Glucose; Inhibitors; Kidney; Phlorizin; Proximal tubule; Review; SGLTs; Type 2 diabetes mellitus.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Design
  • Glucose / metabolism*
  • Glucose Transporter Type 2 / genetics
  • Glucose Transporter Type 2 / physiology*
  • Glycosuria / metabolism
  • HEK293 Cells
  • Homeostasis
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Kidney / metabolism*
  • Kidney Tubules / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Mice
  • Mice, Knockout
  • Phlorhizin / pharmacology
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / physiology*
  • Sodium-Glucose Transporter 2 / genetics
  • Sodium-Glucose Transporter 2 / physiology*
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology


  • Blood Glucose
  • Glucose Transporter Type 2
  • Hypoglycemic Agents
  • SLC2A2 protein, human
  • SLC5A1 protein, human
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Phlorhizin
  • Glucose