| Authors |
Vallon V, Rose M, Gerasimova M, Satriano J, Platt KA, Koepsell H, Cunard R,
Sharma K, Thomson SC, Rieg T
|
| Submitted By |
Kumar Sharma on 3/7/2013 |
| Status |
Published |
| Journal |
American journal of physiology. Renal physiology |
| Year |
2013 |
| Date Published |
1/15/2013 |
| Volume : Pages |
304 : F156 - F167 |
| PubMed Reference |
23152292 |
| Abstract |
The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the
early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic
drugs. We used gene-targeted Sglt2 knockout (Sglt2(-/-)) mice to elucidate the
contribution of SGLT2 to blood glucose control, glomerular hyperfiltration,
kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after
induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did
not affect renal mRNA expression of glucose transporters SGLT1, NaGLT1, GLUT1,
or GLUT2 in response to STZ. Application of STZ increased blood glucose levels
to a lesser extent in Sglt2(-/-) vs. wild-type (WT) mice (~300 vs. 470 mg/dl)
but increased glucosuria and food and fluid intake to similar levels in both
genotypes. Lack of SGLT2 prevented STZ-induced glomerular hyperfiltration but
not the increase in kidney weight. Knockout of SGLT2 attenuated the STZ-induced
renal accumulation of p62/sequestosome, an indicator of impaired autophagy, but
did not attenuate the rise in renal expression of markers of kidney growth (p27
and proliferating cell nuclear antigen), oxidative stress (NADPH oxidases 2 and
4 and heme oxygenase-1), inflammation (interleukin-6 and monocyte
chemoattractant protein-1), fibrosis (fibronectin and Sirius red-sensitive
tubulointerstitial collagen accumulation), or injury (renal/urinary neutrophil
gelatinase-associated lipocalin). SGLT2 deficiency did not induce ascending
urinary tract infection in nondiabetic or diabetic mice. The results indicate
that SGLT2 is a determinant of hyperglycemia and glomerular hyperfiltration in
STZ-induced diabetes mellitus but is not critical for the induction of renal
growth and markers of renal injury, inflammation, and fibrosis.
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