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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 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.
  • |*Models, Biological [MESH]
  • |Animals [MESH]
  • |Diabetic Nephropathies/*metabolism [MESH]
  • |Glomerular Filtration Rate/physiology [MESH]
  • |Nephrons/*metabolism [MESH]
  • |Oxygen Consumption/*physiology [MESH]
  • |Rats [MESH]
  • |Sodium-Glucose Transporter 2 Inhibitors [MESH]


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