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10.1152/ajprenal.00543.2015

http://scihub22266oqcxt.onion/10.1152/ajprenal.00543.2015
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suck abstract from ncbi


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pmid26764207      Am+J+Physiol+Renal+Physiol 2016 ; 310 (11): F1269-83
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  • 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 PMID26764207show 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 QO2active 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 QO2active by 5?12% in the cortex and medulla. Diabetes increases overall TNa and QO2active by ?50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers QO2active in the cortex by ?30%, due to GFR reduction that lowers proximal tubule active TNa, but raises QO2active in the medulla by ?7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase QO2active 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 QO2active by 33% in S3 segments, and raises QO2active by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical QO2active and raises medullary QO2active, particularly in S3 segments.
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