scholarly journals Integrin α1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy

2012 ◽  
Vol 81 (11) ◽  
pp. 1086-1097 ◽  
Author(s):  
Ling Yu ◽  
Yan Su ◽  
Paisit Paueksakon ◽  
Huifang Cheng ◽  
Xiwu Chen ◽  
...  
PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69193 ◽  
Author(s):  
Sih Min Tan ◽  
Arpeeta Sharma ◽  
Derek Y. C. Yuen ◽  
Nada Stefanovic ◽  
Guy Krippner ◽  
...  

Author(s):  
AC Langheinrich ◽  
D Sedding ◽  
M Kampschulte ◽  
J Wilhelm ◽  
W Haberbosch ◽  
...  

2014 ◽  
Vol 306 (2) ◽  
pp. F188-F193 ◽  
Author(s):  
Timo Rieg ◽  
Takahiro Masuda ◽  
Maria Gerasimova ◽  
Eric Mayoux ◽  
Kenneth Platt ◽  
...  

In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted.


2011 ◽  
Vol 21 (9-10) ◽  
pp. 676-677
Author(s):  
V. Schoewel ◽  
S. Adams ◽  
C. Herrmann ◽  
U. Zacharias ◽  
M. Boschmann ◽  
...  

2004 ◽  
Vol 164 (6) ◽  
pp. 2279-2288 ◽  
Author(s):  
Derek Paisley ◽  
Stephen Banks ◽  
Jim Selfridge ◽  
Neil F. McLennan ◽  
Ann-Marie Ritchie ◽  
...  

2021 ◽  
pp. 108680
Author(s):  
Ranganathan Arunkumar ◽  
Aruna Gorusupudi ◽  
Binxing Li ◽  
J. David Blount ◽  
Uzoamaka Nwagbo ◽  
...  

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