Access the full text.
Sign up today, get DeepDyve free for 14 days.
T. Rieg, T. Masuda, Maria Gerasimova, E. Mayoux, K. Platt, D. Powell, S. Thomson, H. Koepsell, V. Vallon (2014)
Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia.American journal of physiology. Renal physiology, 306 2
W. Faquin, T. Schneider, M. Goldberg (1992)
EFFECT OF INFLAMMATORY CYTOKINES ON HYPOXIA-INDUCED ERYTHROPOIETIN PRODUCTIONBlood, 79
Simeon Taylor, J. Blau, K. Rother (2015)
Possible adverse effects of SGLT2 inhibitors on bone.The lancet. Diabetes & endocrinology, 3 1
V. Vallon, J. Schwark, K. Richter, M. Hropot (2000)
Role of Na(+)/H(+) exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3.American journal of physiology. Renal physiology, 278 3
Y. You, T. Quach, Rintaro Saito, Jessica Pham, K. Sharma (2016)
Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN, 27 2
P. Schultheis, L. Clarke, P. Meneton, Marian Miller, M. Soleimani, Lara Gawenis, Tara Riddle, J. Duffy, T. Doetschman, Tong Wang, G. Giebisch, P. Aronson, J. Lorenz, G. Shull (1998)
Renal and intestinal absorptive defects in mice lacking the NHE3 Na +/H+ exchangerNature Genetics, 19
J. O'Neill, A. Fasching, Liselotte Pihl, D. Patinha, S. Franzén, F. Palm (2015)
Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats.American journal of physiology. Renal physiology, 309 3
W Huang, R Patel, A Onishi, M Crespo-Masip, M Soleimani, B Freeman, V Vallon (2018)
Tubular NHE3 is a determinant of the acute natriuretic and chronic blood pressure lowering effect of the SGLT2 inhibitor empagliflozin, 32
T. Pessoa, L. Campos, L. Carraro-Lacroix, A. Girardi, G. Malnic (2014)
Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule.Journal of the American Society of Nephrology : JASN, 25 9
D. Litvinov, K. Selvarajan, M. Garelnabi, L. Brophy, S. Parthasarathy (2010)
Anti-atherosclerotic actions of azelaic acid, an end product of linoleic acid peroxidation, in mice.Atherosclerosis, 209 2
B. Zinman, C. Wanner, J. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O. Johansen, H. Woerle, U. Broedl, S. Inzucchi (2015)
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.The New England journal of medicine, 373 22
Roberto Collazo, Lingzhi Fan, M. Hu, Hui Zhao, M. Wiederkehr, O. Moe (2000)
Acute Regulation of Na+/H+ Exchanger NHE3 by Parathyroid Hormone via NHE3 Phosphorylation and Dynamin-dependent Endocytosis*The Journal of Biological Chemistry, 275
K. Sharma, Bethany Karl, A. Mathew, J. Gangoiti, C. Wassel, Rintaro Saito, Minya Pu, Shoba Sharma, Y. You, Lin Wang, M. Diamond-Stanic, M. Lindenmeyer, C. Forsblom, Wei Wu, J. Ix, T. Ideker, J. Kopp, S. Nigam, C. Cohen, P. Groop, B. Barshop, L. Natarajan, W. Nyhan, R. Naviaux (2013)
Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease.Journal of the American Society of Nephrology : JASN, 24 11
M. Goicoechea, J. Martin, P. Sequera, J. Quiroga, A. Ortiz, V. Carreño, C. Caramelo (1998)
Role of cytokines in the response to erythropoietin in hemodialysis patients.Kidney international, 54 4
M. Coady, Abdulah Tarazi, R. Santer, P. Bissonnette, Louis Sasseville, J. Calado, Yoann Lussier, C. Dumayne, D. Bichet, J. Lapointe (2017)
MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2.Journal of the American Society of Nephrology : JASN, 28 1
M. Yılmaz, Y. Solak, A. Covic, D. Goldsmith, M. Kanbay (2011)
Renal Anemia of Inflammation: The Name Is Self-ExplanatoryBlood Purification, 32
A. Onishi, Yiling Fu, Manjula Darshi, Maria Crespo‐Masip, Winnie Huang, Pan-ai Song, Rohit Patel, Young Kim, Josselin Nespoux, Brent Freeman, M. Soleimani, S. Thomson, K. Sharma, V. Vallon (2019)
Effect of Renal Tubule-Specific Knockdown of the Na+/H+ Exchanger NHE3 in Akita Diabetic Mice.American journal of physiology. Renal physiology
T. Thach, Chunyan Wu, K. Hwang, Sung-Joon Lee (2020)
Azelaic Acid Induces Mitochondrial Biogenesis in Skeletal Muscle by Activation of Olfactory Receptor 544Frontiers in Physiology, 11
V. Vallon (2020)
Glucose transporters in the kidney in health and diseasePflügers Archiv - European Journal of Physiology, 472
Kelsey Fisher-Wellman, T. Weber, Brook Cathey, Patricia Brophy, Laura Gilliam, Constance Kane, J. Maples, T. Gavin, J. Houmard, P. Neufer (2013)
Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese HumansDiabetes, 63
H. Kocinsky, D. Dynia, Tong Wang, P. Aronson (2007)
NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity.American journal of physiology. Renal physiology, 293 1
J. Lorenz, P. Schultheis, T. Traynor, G. Shull, J. Schnermann (1999)
Micropuncture analysis of single-nephron function in NHE3-deficient mice.American journal of physiology. Renal physiology, 277 3
B. Neal, V. Perkovic, K. Mahaffey, D. Zeeuw, G. Fulcher, N. Erondu, Wayne Shaw, G. Law, Mehul Desai, D. Matthews (2017)
Canagliflozin and Cardiovascular and Renal Events in Type 2 DiabetesThe New England Journal of Medicine, 377
Yiling Fu, D. Breljak, A. Onishi, F. Batz, Rohit Patel, Winnie Huang, Pan-ai Song, Brent Freeman, E. Mayoux, H. Koepsell, N. Anzai, S. Nigam, I. Sabolić, V. Vallon (2018)
Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin.American journal of physiology. Renal physiology, 315 2
Joo Choi, Mehul Shah, Min Lee, P. Schultheis, G. Shull, S. Muallem, Michel Baum (2000)
Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule.The Journal of clinical investigation, 105 8
H. Kocinsky, A. Girardi, D. Biemesderfer, Thao Nguyen, S. Mentone, J. Orlowski, P. Aronson (2005)
Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites.American journal of physiology. Renal physiology, 289 2
A. Weinstein (1986)
Osmotic diuresis in a mathematical model of the rat proximal tubule.The American journal of physiology, 250 5 Pt 2
P. Grimm, Yoskaly Lazo-Fernandez, E. Delpire, S. Wall, S. Dorsey, E. Weinman, R. Coleman, J. Wade, P. Welling (2015)
Integrated compensatory network is activated in the absence of NCC phosphorylation.The Journal of clinical investigation, 125 5
R. Faulhaber-Walter, Limeng Chen, M. Oppermann, S. Kim, Yuning Huang, Noriyuki Hiramatsu, D. Mizel, H. Kajiyama, P. Zerfas, J. Briggs, J. Kopp, J. Schnermann (2008)
Lack of A1 adenosine receptors augments diabetic hyperfiltration and glomerular injury.Journal of the American Society of Nephrology : JASN, 19 4
S. Hallan, M. Afkarian, L. Zelnick, B. Kestenbaum, Shoba Sharma, Rintaro Saito, Manjula Darshi, G. Barding, D. Raftery, W. Ju, M. Kretzler, K. Sharma, I. Boer (2017)
Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD PatientsEBioMedicine, 26
Natsuko Tokonami, L. Morla, G. Centeno, D. Mordasini, S. Ramakrishnan, S. Nikolaeva, C. Wagner, O. Bonny, P. Houillier, A. Doucet, D. Firsov (2013)
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism.The Journal of clinical investigation, 123 7
Yi Duan, A. Weinstein, S. Weinbaum, Tong Wang (2010)
Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cellsProceedings of the National Academy of Sciences, 107
K. Finberg, C. Wagner, M. Bailey, T. Paunescu, S. Breton, Dennis Brown, G. Giebisch, J. Geibel, R. Lifton (2005)
The B1-subunit of the H(+) ATPase is required for maximal urinary acidification.Proceedings of the National Academy of Sciences of the United States of America, 102 38
P. Schlatter, C. Beglinger, J. Drewe, H. Gutmann (2007)
Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cellsRegulatory Peptides, 141
R. Packer, C. Curry, K. Brown (1995)
Urinary organic anion excretion in response to dietary acid and base loading.Journal of the American Society of Nephrology : JASN, 5 8
L. Taylor, N. Curthoys (2004)
Glutamine metabolism: Role in acid‐base balance *Biochemistry and Molecular Biology Education, 32
V. Vallon, S. Thomson (2017)
Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibitionDiabetologia, 60
M. Bouchard, A. Souabni, M. Busslinger (2004)
Tissue‐specific expression of cre recombinase from the Pax8 locusgenesis, 38
Rong Lin, R. Murtazina, B. Cha, M. Chakraborty, Rafiquel Sarker, Tian-e Chen, Zhihong Lin, B. Hogema, H. Jonge, U. Seidler, J. Turner, Xuhang Li, O. Kovbasnjuk, M. Donowitz (2011)
D-glucose acts via sodium/glucose cotransporter 1 to increase NHE3 in mouse jejunal brush border by a Na+/H+ exchange regulatory factor 2-dependent process.Gastroenterology, 140 2
R. Crajoinas, J. Polidoro, Carla Morais, R. Castelo-Branco, A. Girardi (2016)
Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells.American journal of physiology. Cell physiology, 311 5
J. Brasen, James Burford, A. McDonough, N. Holstein-Rathlou, J. Peti-Peterdi (2014)
Local pH domains regulate NHE3-mediated Na⁺ reabsorption in the renal proximal tubule.American journal of physiology. Renal physiology, 307 11
J. Turner, E. Black (2001)
NHE3-dependent cytoplasmic alkalinization is triggered by Na(+)-glucose cotransport in intestinal epithelia.American journal of physiology. Cell physiology, 281 5
E. Wright, D. Loo, B. Hirayama (2011)
Biology of human sodium glucose transporters.Physiological reviews, 91 2
S. Mulder, H. Heerspink, Manjula Darshi, J. Kim, G. Laverman, K. Sharma, M. Pena (2019)
Effects of dapagliflozin on urinary metabolites in people with type 2 diabetesDiabetes, 21
I. Weiner, J. Verlander (2017)
Ammonia Transporters and Their Role in Acid-Base Balance.Physiological reviews, 97 2
J. Peti-Peterdi (2013)
Mitochondrial TCA cycle intermediates regulate body fluid and acid-base balance.The Journal of clinical investigation, 123 7
Chunyan Wu, Su Hwang, Yaoyao Jia, J. Choi, Y. Kim, Dahee Choi, Duleepa Pathiraja, In-Geol Choi, S. Koo, Sung-Joon Lee (2017)
Olfactory receptor 544 reduces adiposity by steering fuel preference toward fatsJournal of Clinical Investigation, 127
V. Vallon, J. Schroth, J. Satriano, R. Blantz, S. Thomson, T. Rieg (2009)
Adenosine A1 Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes MellitusNephron Physiology, 111
Takahiro Masuda, Yuko Watanabe, Keiko Fukuda, Minami Watanabe, A. Onishi, Ken Ohara, T. Imai, H. Koepsell, S. Muto, V. Vallon, D. Nagata (2018)
Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat.American journal of physiology. Renal physiology, 315 3
V. Vallon, Maria Gerasimova, Michael Rose, T. Masuda, J. Satriano, E. Mayoux, H. Koepsell, S. Thomson, T. Rieg (2014)
SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice.American journal of physiology. Renal physiology, 306 2
I. Bobulescu, O. Moe (2009)
Luminal Na+/H+ exchange in the proximal tubulePflügers Archiv - European Journal of Physiology, 458
M. Gekle, K. Völker, S. Mildenberger, R. Freudinger, G. Shull, M. Wiemann (2004)
NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo.American journal of physiology. Renal physiology, 287 3
P. Grimm, P. Welling (2017)
&agr;-Ketoglutarate drives electroneutral NaCl reabsorption in intercalated cells by activating a G-protein coupled receptor, Oxgr1Current Opinion in Nephrology and Hypertension, 26
A. Layton, V. Vallon (2018)
SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism.American journal of physiology. Renal physiology, 314 5
A. Girardi, F. Sole (2012)
Deciphering the mechanisms of the Na+/H+ exchanger-3 regulation in organ dysfunction.American journal of physiology. Cell physiology, 302 11
Tong Wang, Chao-Ling Yang, T. Abbiati, P. Schultheis, G. Shull, G. Giebisch, P. Aronson (1999)
Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice.The American journal of physiology, 277 2
H. Qiu, Aleksandra Novikov, V. Vallon (2017)
Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectivesDiabetes/Metabolism Research and Reviews, 33
V. Vallon, S. Thomson (2020)
The tubular hypothesis of nephron filtration and diabetic kidney diseaseNature Reviews Nephrology, 16
O. Beloto-Silva, U. Machado, M. Oliveira‐Souza (2011)
Glucose-Induced Regulation of NHEs Activity and SGLTs Expression Involves the PKA Signaling PathwayThe Journal of Membrane Biology, 239
L. Veiras, A. Girardi, Joshua Curry, L. Pei, D. Ralph, An Tran, R. Castelo-Branco, N. Pastor-Soler, C. Arranz, A. Yu, A. McDonough (2017)
Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.Journal of the American Society of Nephrology : JASN, 28 12
C. Wanner, S. Inzucchi, J. Lachin, D. Fitchett, M. Eynatten, M. Mattheus, O. Johansen, H. Woerle, U. Broedl, B. Zinman (2016)
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.The New England journal of medicine, 375 4
P. Quinn, D. Yeagley (2005)
Insulin regulation of PEPCK gene expression: a model for rapid and reversible modulation.Current drug targets. Immune, endocrine and metabolic disorders, 5 4
A. Woo, W. Noonan, P. Schultheis, J. Neumann, Patrice Manning, J. Lorenz, G. Shull (2003)
Renal function in NHE3-deficient mice with transgenic rescue of small intestinal absorptive defect.American journal of physiology. Renal physiology, 284 6
T. Rieg, Maria Gerasimova, F. Murray, T. Masuda, T. Tang, Michael Rose, D. Drucker, V. Vallon (2012)
Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice.American journal of physiology. Renal physiology, 303 7
Kavee Limbutara, C. Chou, M. Knepper (2020)
Quantitative Proteomics of All 14 Renal Tubule Segments in Rat.Journal of the American Society of Nephrology : JASN
V. Vallon, Michael Rose, Maria Gerasimova, J. Satriano, K. Platt, H. Koepsell, R. Cunard, K. Sharma, S. Thomson, T. Rieg (2013)
Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus.American journal of physiology. Renal physiology, 304 2
D. Scott, R. O’Doherty, J. Stafford, C. Newgard, D. Granner (1998)
The Repression of Hormone-activated PEPCK Gene Expression by Glucose Is Insulin-independent but Requires Glucose Metabolism*The Journal of Biological Chemistry, 273
M. Coady, B. Wallendorff, J. Lapointe (2017)
Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na+-glucose cotransporter.American journal of physiology. Renal physiology, 313 2
Hong Li, Zhaopeng Du, Sharon Barone, I. Rubera, A. McDonough, M. Tauc, K. Zahedi, Tong Wang, M. Soleimani (2013)
Proximal tubule specific knockout of the Na+/H+ exchanger NHE3: effects on bicarbonate absorption and ammonium excretionJournal of Molecular Medicine (Berlin, Germany), 91
R. Crajoinas, F. Oricchio, T. Pessoa, Bruna Pacheco, L. Lessa, G. Malnic, A. Girardi (2011)
Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1.American journal of physiology. Renal physiology, 301 2
M. Lowry, B. Ross (1980)
Activation of oxoglutarate dehydrogenase in the kidney in response to acute acidosis.The Biochemical journal, 190 3
Y Fu, M Gerasimova, E Mayoux, T Masuda, V Vallon (2014)
SGLT2 inhibitor empagliflozin increases renal NHE3 phosphorylation in diabetic Akita mice: possible implications for the prevention of glomerular hyperfiltration, 63
V. Vallon, J. Schroth, K. Platt, J. Whaley, S. Thomson, T. Rieg (2010)
SGLT2 mediates glucose reabsorption in the early proximal tubuleThe FASEB Journal, 24
J. Blau, V. Bauman, E. Conway, P. Piaggi, M. Walter, E. Wright, Shanna Bernstein, A. Courville, M. Collins, K. Rother, Simeon Taylor (2018)
Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study.JCI insight, 3 8
A. Layton, V. Vallon, A. Edwards (2015)
Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition.American journal of physiology. Renal physiology, 308 12
Huiren Zhao, Harn Shiue, Sara Palkon, Yingmin Wang, P. Cullinan, J. Burkhardt, M. Musch, E. Chang, J. Turner (2004)
Ezrin regulates NHE3 translocation and activation after Na+-glucose cotransport.Proceedings of the National Academy of Sciences of the United States of America, 101 25
Inhibitors of the proximal tubular sodium glucose cotransporter SGLT2 are natriuretic and they lower blood pressure. There are reports that the activities of SGLT2 and the Na+-H+-exchanger, NHE3, are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of the SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in non-diabetic mice with tubule-specific NHE3 knock-down (NHE3-ko) and wild-type littermates (WT). A single dose of empagliflozin, titrated to cause minimal glucosuria, increased urinary excretion of Na+ and bicarbonate, and raised urine pH in WT, but not in NHE3-ko. Chronic empagliflozin treatment tended to lower SBP despite higher renal renin mRNA expression, and lowered the ratio of SBP to renin mRNA, indicating volume loss. This effect of empagliflozin depended on tubular NHE3. In diabetic Akita mice, chronic empagliflozin enhanced phosphorylation of NHE3 (S552/S605), changes previously linked to lesser NHE3-mediated reabsorption. Chronic empagliflozin also increased expression of genes involved with renal gluconeogenesis, bicarbonate regeneration, and ammonium formation. While this could reflect compensatory responses to acidification of proximal tubular cells resulting from reduced NHE3 activity, these effects were at least in part independent of tubular NHE3 and potentially indicated metabolic adaptations to urinary glucose loss. Moreover, empagliflozin increased luminal α-ketoglutarate, which may serve to stimulate compensatory distal NaCl reabsorption, while co-generated and excreted ammonium balances urine losses of this "potential bicarbonate". The data implicate NHE3 as a determinant of the natriuretic effect of empagliflozin.
American Journal of Physiology-Renal Physiology – The American Physiological Society
Published: Oct 1, 2020
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.