Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

American Journal of Physiology. Renal Physiology
Anita T LaytonAurélie Edwards

Abstract

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...Continue Reading

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Citations

Jun 10, 2016·Mathematical Medicine and Biology : a Journal of the IMA·Ioannis SgouralisAnita T Layton
Jan 19, 2017·Diabetes/metabolism Research and Reviews·Hongyu QiuVolker Vallon
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Anita T LaytonVolker Vallon
Sep 25, 2017·The Journal of Physiology·Khalil UdwanEric Feraille
Jan 25, 2018·American Journal of Physiology. Renal Physiology·Anita T Layton, Volker Vallon
Mar 31, 2017·American Journal of Physiology. Renal Physiology·Ying ChenAnita T Layton
Oct 22, 2016·American Journal of Physiology. Renal Physiology·Anita T LaytonAurélie Edwards
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Anita T Layton
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Mar 2, 2018·Internal Medicine·Marie Ito, Tetsuhiro Tanaka
Jul 18, 2018·Current Opinion in Nephrology and Hypertension·Anita T Layton, Volker Vallon
May 31, 2018·American Journal of Physiology. Renal Physiology·Qianyi LiAnita T Layton
Dec 20, 2018·American Journal of Physiology. Renal Physiology·Anita T Layton, Jennifer C Sullivan
Feb 6, 2019·International Journal of Molecular Sciences·Tuba M AnsaryAkira Nishiyama
Jun 6, 2019·American Journal of Physiology. Renal Physiology·Akira OnishiVolker Vallon
Jan 20, 2017·American Journal of Physiology. Renal Physiology·Anita T Layton
Dec 10, 2019·Current Opinion in Nephrology and Hypertension·Josselin Nespoux, Volker Vallon
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Feb 11, 2020·American Journal of Physiology. Renal Physiology·Sameed Ahmed, Anita T Layton
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Sep 14, 2017·Bulletin of Mathematical Biology·Aurélie Edwards, Anita T Layton
Aug 23, 2018·Diabetologia·Timo Rieg, Volker Vallon
Feb 21, 2019·American Journal of Physiology. Renal Physiology·Aurélie EdwardsOlivier Bonny
Dec 15, 2019·International Journal of Molecular Sciences·Vivien AubertPatrick Hannaert
Jul 2, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Angelamellisy Revelian NdibalemaQiuling Fan
Jun 30, 2018·Biological cybernetics·Anita T Layton
Oct 28, 2019·American Journal of Physiology. Renal Physiology·Aurélie Edwards, Alicia A McDonough
Aug 7, 2019·Diabetes Technology & Therapeutics·Takashi MaruyamaMasanori Abe
Dec 4, 2019·American Journal of Physiology. Renal Physiology·Aurélie EdwardsAnita T Layton
Oct 1, 2019·American Journal of Physiology. Renal Physiology·Rui HuAnita T Layton
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