Expression and Activity of SGLT2 in Diabetes Induced by Streptozotocin: Relationship with the Lipid Environment

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 α-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.

Sodium glucose cotransporter SGLT1 as a therapeutic target in diabetes mellitus

“…Other studies found unchanged renal SGLT1 protein expression [114-116] or reduced renal expression and activity of SGLT1 [117] in diabetic rodent models. Using Sglt1 −/− mice as a critical negative control for the antibody, renal membrane protein expression of SGLT1 was found to be reduced in Akita mice, a genetic model of T1DM [107].…”

Renal Function in Diabetic Disease Models: The Tubular System in the Pathophysiology of the Diabetic Kidney

“…Diabetes may not uniformly increase renal expression of SGLTs because some studies found unchanged or even reduced renal SGLT expression and/or activity in diabetic rodent models (19, 56, 57). Studies in primary cultures of renal proximal tubule cells indicated that high-glucose-induced oxidative stress can reduce SGLT expression and activity (Figure 3) (58).…”

Empagliflozin: a new strategy for nephroprotection in diabetes

“…Снижение экспрессии SGLT2 в почках зафиксировано при стрептозотоциновом СД (модель СД1) у мышей линии C57BL/6 [11] и у крыс линии Wistar [14]. В другом исследовании зафиксировано повышение экспрессии SGLT2 как на фоне высокосолевой диеты, так и на фоне диеты с нормальным содержанием натрия в данной модели СД [15].…”