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


CONCLUSIONS
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.
Albertoni Borghese
María F
MF
Cátedra de Biología Celular, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. mfalber@ffyb.uba.ar
Majowicz
Mónica P
MP
Ortiz
María C
MC
Passalacqua
María del Rosario
Mdel R
Sterin Speziale
Norma B
NB
Vidal
Norberto A
NA
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*; D013311:Streptozocin
D010743:Phospholipids; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D013311:Streptozocin