Expresion acute; and activity of SGLT2 in diabetes induced by streptozotocin : relationship with the lipid environment.

FLORENCIA ALBERTONI BORGHESE; MÓNICA MAJOWICZ; MARÍA DEL CARMEN ORTIZ; MARÍA DEL ROSARIO PASSALAQUA; NORMA B STERIN-SPEZIALE; NORBERTO A VIDAL

NEPHRON PHYSIOLOGY

KARGER

Año: 2009 vol. 112 p. 45 - 52

1660-2137

Abstract 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 ƒ¿-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Ls 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 vs. control, without differences in phosphatidylinostol (PI), phosphatidylserine (PS) and phosphatidylethanolamine (PE). Conclusion: The down regulation 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.