Expression and activity of SGLT2 in diabetes induced by streptozotocin: relationship with the lipid environment

Nephron Physiol. 2009;112(3):p45-52. doi: 10.1159/000214214. Epub 2009 Apr 24.


Background/aims: Diabetes mellitus may impact on the regulation of renal Na+-glucose cotransporter type 2 (SGLT2), however, previous studies have yielded conflicting results on the effects of streptozotocin (STZ)-induced diabetes on SGLT-mediated glucose transport.

Methods: Diabetes was induced in male Wistar rats. The studies were performed at 3 (D3), 7 (D7) and 14 (D14) days after a single i.p. injection of STZ. SGLT2 activity was measured using alpha-14C-methyl glucose uptake in brush-border vesicles (BBV) from renal cortex, and SGLT2 expression was assessed by immunoblotting. Phospholipids were quantified by a modification of Fiske-Subarow's method after being separated by thin-layer chromatography.

Results: Glucose uptake was reduced in all groups of diabetic rats. SGLT2 expression decreased in D3 and D7. There was a decrease in sphingomyelin (SM) content and an increase in phosphatidylcholine (PC) content in BBV from D14 versus control, without differences in phosphatidylinositol (PI), phosphatidylserine (PS) and phosphatidylethanolamine (PE).

Conclusion: The downregulation of SGLT2 activity during STZ-induced diabetes may be a protective mechanism to control the excess of circulating glucose and could be a consequence of a decrease in SGLT2 expression in D3 and D7, whereas altered activity of SGLT2 in D14 could be a consequence of changes in membrane lipid composition. However, we cannot discard the possibility that the decrease in SGLT2 activity could be due to a covalent modification of the active site of the protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / metabolism*
  • Disease Models, Animal*
  • Gene Expression / drug effects
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Phospholipids / metabolism*
  • Rats
  • Rats, Wistar
  • Sodium-Glucose Transporter 2 / metabolism*
  • Streptozocin*


  • Phospholipids
  • Slc5a2 protein, rat
  • Sodium-Glucose Transporter 2
  • Streptozocin