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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 310
(11
): F1269-83
Nephropedia Template TP
gab.com Text
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English Wikipedia
Predicted consequences of diabetes and SGLT inhibition on transport and oxygen
consumption along a rat nephron
#MMPMID26764207
Layton AT
; Vallon V
; Edwards A
Am J Physiol Renal Physiol
2016[Jun]; 310
(11
): F1269-83
PMID26764207
show ga
Diabetes increases the reabsorption of Na(+) (TNa) and glucose via the
sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments)
of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower
hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2
inhibition affect TNa and sodium transport-dependent oxygen consumption [Formula:
see text] along the whole nephron. To do so, we developed a mathematical model of
water and solute transport from the Bowman space to the papillary tip of a
superficial nephron of the rat kidney. Model simulations indicate that, in the
nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all
nephron segments, thereby raising [Formula: see text] by 5-12% in the cortex and
medulla. Diabetes increases overall TNa and [Formula: see text] by ?50 and 100%,
mainly because it enhances glomerular filtration rate (GFR) and transport load.
In diabetes, acute and chronic SGLT2 inhibition lowers [Formula: see text] in the
cortex by ?30%, due to GFR reduction that lowers proximal tubule active TNa, but
raises [Formula: see text] in the medulla by ?7%. In the medulla specifically,
chronic SGLT2 inhibition is predicted to increase [Formula: see text] by 26% in
late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs
(mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and
IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose
excretion, reduces [Formula: see text] by 33% in S3 segments, and raises
[Formula: see text] by <1% in mTAL, OMCD, and IMCD. In summary, the model
predicts that SGLT2 blockade in diabetes lowers cortical [Formula: see text] and
raises medullary [Formula: see text], particularly in S3 segments.