{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:03:13Z","timestamp":1765231393157,"version":"build-2065373602"},"reference-count":131,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HL163844"],"award-info":[{"award-number":["HL163844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hypertension is an important risk factor for cardiovascular diseases. High salt intake when consumed with excess fructose enhances hypertension and resultant cardiovascular disease. Usually, the small intestine absorbs dietary fructose, and the proximal tubule of kidney reabsorbs filtered fructose into the circulation with the help of different transporters including SGLT4 and SGLT5. Very recently, SGLT5 mRNA has also been found to be expressed in the heart. High-fructose diet stimulates the sympathetic nervous system and renin\u2013angiotensin\u2013aldosterone (RAAS) activity, of which both are responsible for endothelial dysfunction and are associated with salt-sensitive hypertension. Few studies exist regarding the effects of SGLT4 and SGLT5 on cardiovascular function and blood pressure. However, SGLT4 gene knockout does not alter fructose-associated impact on blood pressure. In contrast, blood pressure does not increase in SGLT5 knockout rats even during fructose consumption. Given that limiting fructose and salt consumption as a public health strategy has proven challenging, we hope that studies into SGLT4 and SGLT5 transporters will open new research initiatives to address salt-sensitive hypertension and cardiovascular disease. This review highlights current information about SGLT4 and SGLT5 on fructose absorption, salt-sensitive hypertension, cardiovascular disease and points the way for the development of therapeutic fructose inhibitors that limit adverse effects.<\/jats:p>","DOI":"10.3390\/nu17152511","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T08:51:41Z","timestamp":1754038301000},"page":"2511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-4994","authenticated-orcid":false,"given":"Sharif Hasan","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Department of Physiology, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5886-427X","authenticated-orcid":false,"given":"Noreen F.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S748","DOI":"10.1093\/ajcn\/58.5.748S","article-title":"Fructose absorption","volume":"58","author":"Riby","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1096\/fasebj.4.9.2189777","article-title":"Metabolic effects of dietary fructose","volume":"4","author":"Hallfrisch","year":"1990","journal-title":"FASEB J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pereira, R.M., Botezelli, J.D., da Cruz Rodrigues, K.C., Mekary, R.A., Cintra, D.E., Pauli, J.R., da Silva, A.S.R., Ropelle, E.R., and de Moura, L.P. (2017). Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism. Nutrients, 9.","DOI":"10.3390\/nu9040405"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1172\/JCI96702","article-title":"Fructose metabolism and metabolic disease","volume":"128","author":"Hannou","year":"2018","journal-title":"J. Clin. Investg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Taskinen, M.R., Packard, C.J., and Bor\u00e9n, J. (2019). Dietary Fructose and the Metabolic Syndrome. Nutrients, 11.","DOI":"10.3390\/nu11091987"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/j.cmet.2021.09.010","article-title":"Molecular aspects of fructose metabolism and metabolic disease","volume":"33","author":"Herman","year":"2021","journal-title":"Cell Metab."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Busnatu, S.S., Salmen, T., Pana, M.A., Rizzo, M., Stallone, T., Papanas, N., Popovic, D., Tanasescu, D., Serban, D., and Stoian, A.P. (2022). The Role of Fructose as a Cardiovascular Risk Factor: An Update. Metabolites, 12.","DOI":"10.3390\/metabo12010067"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Siddiqui, S.H., Pitpitan, R., Boychev, B., Komnenov, D., and Rossi, N.F. (2024). Impact of inhibition of the renin-angiotensin system on early cardiac and renal abnormalities in Sprague Dawley rats fed short-term high fructose plus high salt diet. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1436958"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1152\/physrev.00019.2009","article-title":"Metabolic effects of fructose and the worldwide increase in obesity","volume":"90","author":"Tappy","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3945\/an.112.002824","article-title":"Sucrose, high-fructose corn syrup, and fructose, their metabolism and potential health effects: What do we really know?","volume":"4","author":"Rippe","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/ki.2008.184","article-title":"Fructose-induced hypertension: Essential role of chloride and fructose absorbing transporters PAT1 and Glut5","volume":"74","author":"Singh","year":"2008","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1074\/jbc.M808128200","article-title":"Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension","volume":"284","author":"Barone","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1748-1716.2010.02167.x","article-title":"Dietary fructose, salt absorption and hypertension in metabolic syndrome: Towards a new paradigm","volume":"201","author":"Soleimani","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"392708","DOI":"10.4061\/2011\/392708","article-title":"The role of salt in the pathogenesis of fructose-induced hypertension","volume":"2011","author":"Soleimani","year":"2011","journal-title":"Int. J. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000343390","article-title":"Fructose acutely stimulates NHE3 activity in kidney proximal tubule","volume":"36","author":"Crajoinas","year":"2012","journal-title":"Kidney Blood Press. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1161\/HYPERTENSIONAHA.113.02564","article-title":"Fructose stimulates Na\/H exchange activity and sensitizes the proximal tubule to angiotensin II","volume":"63","author":"Cabral","year":"2014","journal-title":"Hypertension"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e15456","DOI":"10.14814\/phy2.15456","article-title":"Dietary fructose and high salt in young male Sprague Dawley rats induces salt-sensitive changes in renal function in later life","volume":"10","author":"Levanovich","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13162","DOI":"10.14814\/phy2.13162","article-title":"Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide","volume":"5","author":"Gordish","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1097\/HJH.0000000000000551","article-title":"The mechanisms underlying fructose-induced hypertension: A review","volume":"33","author":"Klein","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R529","DOI":"10.1152\/ajpregu.00020.2018","article-title":"Bilateral renal cryodenervation decreases arterial pressure and improves insulin sensitivity in fructose-fed Sprague-Dawley rats","volume":"315","author":"Soncrant","year":"2018","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1161\/HYPERTENSIONAHA.118.12150","article-title":"Multilayered Interplay Between Fructose and Salt in Development of Hypertension","volume":"73","author":"Eren","year":"2019","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fukuzawa, T., Fukazawa, M., Ueda, O., Shimada, H., Kito, A., Kakefuda, M., Kawase, Y., Wada, N.A., Goto, C., and Fukushima, N. (2013). SGLT5 reabsorbs fructose in the kidney but its deficiency paradoxically exacerbates hepatic steatosis induced by fructose. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056681"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s13300-010-0006-4","article-title":"Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members","volume":"1","author":"Chen","year":"2010","journal-title":"Diabetes Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1161\/HYPERTENSIONAHA.123.22535","article-title":"Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension","volume":"81","author":"Forester","year":"2024","journal-title":"Hypertension"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/s41440-024-01915-0","article-title":"Possible involvement of up-regulated salt-dependent glucose transporter-5 (SGLT5) in high-fructose diet-induced hypertension","volume":"48","author":"Hara","year":"2025","journal-title":"Hypertens. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.febslet.2011.12.027","article-title":"Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter","volume":"586","author":"Grempler","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/nutrit\/nuw028","article-title":"Salt-sensitive hypertension: Mechanisms and effects of dietary and other lifestyle factors","volume":"74","author":"Pilic","year":"2016","journal-title":"Nutr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.freeradbiomed.2015.11.009","article-title":"Dietary (-)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats","volume":"90","author":"Prince","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Levanovich, P.E., Chung, C.S., Komnenov, D., and Rossi, N.F. (2021). Fructose plus High-Salt Diet in Early Life Results in Salt-Sensitive Cardiovascular Changes in Mature Male Sprague Dawley Rats. Nutrients, 13.","DOI":"10.3390\/nu13093129"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.soard.2016.04.022","article-title":"Sodium glucose transport modulation in type 2 diabetes and gastric bypass surgery","volume":"12","author":"Baud","year":"2016","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1152\/physrev.00055.2009","article-title":"Biology of human sodium glucose transporters","volume":"91","author":"Wright","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.abb.2008.11.008","article-title":"Human sodium\/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells","volume":"481","author":"Lin","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/MNH.0000000000000152","article-title":"Sodium-glucose cotransport","volume":"24","author":"Poulsen","year":"2015","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_34","unstructured":"Chackalamannil, S., Rotella, D., and Ward, S.E. (2017). 7.13-Sodium\u2013Glucose Cotransporters. Comprehensive Medicinal Chemistry III, Elsevier."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00125-016-4157-3","article-title":"Targeting renal glucose reabsorption to treat hyperglycaemia: The pleiotropic effects of SGLT2 inhibition","volume":"60","author":"Vallon","year":"2017","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbrc.2008.11.015","article-title":"Reanalysis of structure\/function correlations in the region of transmembrane segments 4 and 5 of the rabbit sodium\/glucose cotransporter","volume":"378","author":"Liu","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1126\/science.1160406","article-title":"The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+\/sugar symport","volume":"321","author":"Faham","year":"2008","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1038\/s41467-023-38720-1","article-title":"Structures of human SGLT in the occluded state reveal conformational changes during sugar transport","volume":"14","author":"Cui","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41586-021-04212-9","article-title":"Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter","volume":"601","author":"Niu","year":"2022","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.febslet.2007.04.013","article-title":"Transporters for uptake and allocation of organic nitrogen compounds in plants","volume":"581","author":"Rentsch","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41586-021-04211-w","article-title":"Structure and mechanism of the SGLT family of glucose transporters","volume":"601","author":"Han","year":"2022","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.lfs.2004.10.016","article-title":"SLC5A9\/SGLT4, a new Na+-dependent glucose transporter, is an essential transporter for mannose, 1,5-anhydro-D-glucitol, and fructose","volume":"76","author":"Tazawa","year":"2005","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/j.2040-1124.2012.00227.x","article-title":"Role of sodium-glucose transporters in glucose uptake of the intestine and kidney","volume":"3","author":"Harada","year":"2012","journal-title":"J. Diabetes Investig."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kamitori, K., Shirota, M., and Fujiwara, Y. (2022). Structural Basis of the Selective Sugar Transport in Sodium-Glucose Cotransporters. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2022.167464"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00018-023-04884-8","article-title":"SGLT5 is the renal transporter for 1, 5-anhydroglucitol, a major player in two rare forms of neutropenia","volume":"80","author":"Diederich","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/jimd.12509","article-title":"Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: Impact of a mutation in SGLT5","volume":"45","author":"Boulanger","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, M., Maruthur, N.M., Loomis, S.J., Pietzner, M., North, K.E., Mei, H., Morrison, A.C., Friedrich, N., Pankow, J.S., and Nauck, M. (2017). Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02287-x"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Loomis, S.J., K\u00f6ttgen, A., Li, M., Tin, A., Coresh, J., Boerwinkle, E., Gibbs, R., Muzny, D., Pankow, J., and Selvin, E. (2019). Rare variants in SLC5A10 are associated with serum 1,5-anhydroglucitol (1,5-AG) in the Atherosclerosis Risk in Communities (ARIC) Study. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42202-0"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/ng.3809","article-title":"Whole-genome sequencing identifies common-to-rare variants associated with human blood metabolites","volume":"49","author":"Long","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_50","unstructured":"Nidhar, M., and Tewari, A.K. (2025). Chapter 5-Sodium-glucose cotransporter-2 (SGLT2) inhibitors (gliflozins) in diabetes mellitus: Mechanisms and therapeutic insights. Diabetes Mellitus, Academic Press."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/FJC.0000000000001380","article-title":"Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value","volume":"81","author":"Xie","year":"2023","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1016\/j.jacc.2022.03.353","article-title":"Sodium Glucose Cotransporter-2 Inhibition for Acute Myocardial Infarction: JACC Review Topic of the Week","volume":"79","author":"Udell","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/j.clinthera.2023.10.014","article-title":"SGLT2 Inhibitors to Slow Chronic Kidney Disease Progression: A Review","volume":"46","author":"Maxson","year":"2024","journal-title":"Clin. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"C14","DOI":"10.1152\/ajpcell.00388.2010","article-title":"Glucose transport by human renal Na+\/D-glucose cotransporters SGLT1 and SGLT2","volume":"300","author":"Hummel","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0014-5793(02)03058-2","article-title":"GLUT2 is a high affinity glucosamine transporter","volume":"524","author":"Uldry","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mam.2012.07.001","article-title":"The SLC2 (GLUT) family of membrane transporters","volume":"34","author":"Mueckler","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14523","DOI":"10.1016\/S0021-9258(18)42067-4","article-title":"Fructose transporter in human spermatozoa and small intestine is GLUT5","volume":"267","author":"Burant","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/B978-0-12-384947-2.00353-6","article-title":"Glucose: Properties and analysis","volume":"3","author":"Shendurse","year":"2016","journal-title":"Encycl. Food Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15","DOI":"10.26850\/1678-4618eqj.v31.3.2006.p15-21","article-title":"Analysis of the structure and vibrational spectra of glucose and fructose","volume":"31","author":"Ibrahim","year":"2006","journal-title":"Eclet. Quim."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2147\/DMSO.S198968","article-title":"The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders","volume":"12","author":"Mai","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1016\/j.cmet.2021.09.004","article-title":"\u201cSweet death\u201d: Fructose as a metabolic toxin that targets the gut-liver axis","volume":"33","author":"Febbraio","year":"2021","journal-title":"Cell Metab."},{"key":"ref_62","first-page":"e74143","article-title":"Dietary Fructose: A Literature Review of Current Evidence and Implications on Metabolic Health","volume":"16","author":"Agarwal","year":"2024","journal-title":"Cureus"},{"key":"ref_63","first-page":"53","article-title":"Fructose and its derivatives","volume":"7","author":"Barry","year":"1952","journal-title":"Adv. Carbohydr. Chem."},{"key":"ref_64","unstructured":"Alonso-Fern\u00e1ndez, J., Timson, D., Szilagyi, A., Obendorf, R.L., Abdelmalek, M., McGrath, M., Boukra\u00e2, L., Gastrich, M., Haukioja, A., and Jensen, J. (2012). Dietary Sugars: Chemistry, Analysis, Function and Effects, The Royal Society of Chemistry."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1146\/annurev-nutr-082117-051707","article-title":"Intestinal Absorption of Fructose","volume":"38","author":"Ferraris","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/bbrc.1997.7204","article-title":"Functional studies of human GLUT5: Effect of pH on substrate selection and an analysis of substrate interactions","volume":"238","author":"Kane","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"C864","DOI":"10.1152\/ajpcell.00027.2014","article-title":"Fingerprints of hSGLT5 sugar and cation selectivity","volume":"306","author":"Ghezzi","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Iizuka, K. (2023). Recent Progress on Fructose Metabolism-Chrebp, Fructolysis, and Polyol Pathway. Nutrients, 15.","DOI":"10.3390\/nu15071778"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1681\/ASN.2019101015","article-title":"Fructose Production and Metabolism in the Kidney","volume":"31","author":"Nakagawa","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-nutr-062220-025831","article-title":"Dietary Fructose and Fructose-Induced Pathologies","volume":"42","author":"Jung","year":"2022","journal-title":"Annu. Rev. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1042\/bj0311268","article-title":"The metabolism of lactic and pyruvic acids in normal and tumour tissues: Synthesis of carbohydrate","volume":"31","author":"Benoy","year":"1937","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1172\/JCI109182","article-title":"Renal net glucose release in vivo and its contribution to blood glucose in rats","volume":"62","author":"Kida","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1042\/bj0980210","article-title":"Formation of glucose from hexoses, pentoses, polyols and related substances in kidney cortex","volume":"98","author":"Krebs","year":"1966","journal-title":"Biochem. J."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gladding, M., Shen, X., Snyder, M.P., Havel, P.J., and Adams, S.H. (2024). Interindividual Variability in Postprandial Plasma Fructose Patterns in Adults. Nutrients, 16.","DOI":"10.3390\/nu16183079"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/jdi.13255","article-title":"Sodium-glucose cotransporters: Functional properties and pharmaceutical potential","volume":"11","author":"Sano","year":"2020","journal-title":"J. Diabetes Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1758-5996-5-64","article-title":"Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats","volume":"5","author":"Okamoto","year":"2013","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1007\/s00424-014-1619-7","article-title":"Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart","volume":"467","author":"Vrhovac","year":"2015","journal-title":"Pflug. Arch."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s00424-017-2056-1","article-title":"Expression profiling and immunolocalization of Na(+)-D-glucose-cotransporter 1 in mice employing knockout mice as specificity control indicate novel locations and differences between mice and rats","volume":"469","author":"Breljak","year":"2017","journal-title":"Pflug. Arch."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s10695-020-00770-3","article-title":"Sugar transporter genes in grass carp (Ctenopharyngodon idellus): Molecular cloning, characterization, and expression in response to different stocking densities","volume":"46","author":"Liang","year":"2020","journal-title":"Fish. Physiol. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.biopha.2018.10.198","article-title":"Fibroblast growth factor 21 improves glucose homeostasis partially via down-regulation of Na(+)-d-glucose cotransporter SGLT1 in the small intestine","volume":"109","author":"Wang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1021\/pr500833v","article-title":"The impact of high-fat diet on metabolism and immune defense in small intestine mucosa","volume":"14","author":"Friedrich","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.3168\/jds.S0022-0302(05)72953-2","article-title":"Cloning and expression of bovine sodium\/glucose cotransporter SGLT2","volume":"88","author":"Zhao","year":"2005","journal-title":"J. Dairy. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1007\/s00125-018-4656-5","article-title":"Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2","volume":"61","author":"Ghezzi","year":"2018","journal-title":"Diabetologia"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Kosinski, C., Papadakis, G.E., Salamin, O., Kuuranne, T., Nicoli, R., Pitteloud, N., and Zanchi, A. (2024). Effects of empagliflozin on reproductive system in men without diabetes. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64684-3"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s00592-020-01558-w","article-title":"Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes","volume":"57","author":"Bolla","year":"2020","journal-title":"Acta Diabetol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00795-022-00334-9","article-title":"Hepatic expression of sodium-glucose cotransporter 2 (SGLT2) in patients with chronic liver disease","volume":"55","author":"Nakano","year":"2022","journal-title":"Med. Mol. Morphol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1073\/pnas.1733027100","article-title":"A glucose sensor hiding in a family of transporters","volume":"100","author":"Hirayama","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"118974","DOI":"10.1016\/j.lfs.2020.118974","article-title":"Intestinal sodium\/glucose cotransporter 3 expression is epithelial and downregulated in obesity","volume":"267","author":"Casselbrant","year":"2021","journal-title":"Life Sci."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bianchi, L., and Diez-Sampedro, A. (2010). A single amino acid change converts the sugar sensor SGLT3 into a sugar transporter. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010241"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00424-020-02433-x","article-title":"Sodium-coupled glucose transport, the SLC5 family, and therapeutically relevant inhibitors: From molecular discovery to clinical application","volume":"472","author":"Gyimesi","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"F473","DOI":"10.1152\/ajprenal.00247.2018","article-title":"Fructose reabsorption by rat proximal tubules: Role of Na(+)-linked cotransporters and the effect of dietary fructose","volume":"316","author":"Cabral","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1046\/j.1523-1755.1999.00635.x","article-title":"Presence of fructose transporter GLUT5 in the S3 proximal tubules in the rat kidney","volume":"56","author":"Suzuki","year":"1999","journal-title":"Kidney Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/21623945.2018.1516098","article-title":"SGLT6-A pharmacological target for the treatment of obesity?","volume":"7","author":"Eckhardt","year":"2018","journal-title":"Adipocyte"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ymben.2019.09.006","article-title":"Pan-cancer analysis of the metabolic reaction network","volume":"57","author":"Gatto","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1007\/s00424-020-02439-5","article-title":"Glucose transporters in the small intestine in health and disease","volume":"472","author":"Koepsell","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/dom.12578","article-title":"Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition","volume":"18","author":"Rajeev","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"F32","DOI":"10.1152\/ajprenal.00119.2025","article-title":"Gliflozins in hypertension: Basic mechanisms and clinical insights","volume":"329","author":"Rieg","year":"2025","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00424-020-02361-w","article-title":"Glucose transporters in the kidney in health and disease","volume":"472","author":"Vallon","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2147\/IJNRD.S268811","article-title":"SGLT2 Inhibitors: Emerging Roles in the Protection Against Cardiovascular and Kidney Disease Among Diabetic Patients","volume":"13","author":"Nadkarni","year":"2020","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-physiol-031620-095920","article-title":"Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function","volume":"83","author":"Vallon","year":"2021","journal-title":"Annu. Rev. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/advances\/nmaa084","article-title":"Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages and Risk of Cardiovascular Disease: A Meta-Analysis and Systematic Review","volume":"12","author":"Yin","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41574-021-00627-6","article-title":"The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases","volume":"18","author":"Malik","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Shoham, D.A., Durazo-Arvizu, R., Kramer, H., Luke, A., Vupputuri, S., Kshirsagar, A., and Cooper, R.S. (2008). Sugary soda consumption and albuminuria: Results from the National Health and Nutrition Examination Survey, 1999\u20132004. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003431"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Soleimani, M., Barone, S., Luo, H., and Zahedi, K. (2023). Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054294"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1080\/07315724.2014.916237","article-title":"Total fructose intake and risk of hypertension: A systematic review and meta-analysis of prospective cohorts","volume":"33","author":"Jayalath","year":"2014","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e010977","DOI":"10.1161\/JAHA.118.010977","article-title":"Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies","volume":"8","author":"Liu","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e016543","DOI":"10.1161\/JAHA.120.016543","article-title":"High Fructose-Induced Hypertension and Renal Damage Are Exaggerated in Dahl Salt-Sensitive Rats via Renal Renin-Angiotensin System Activation","volume":"10","author":"Xu","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jnutbio.2019.05.017","article-title":"Fructose increases the activity of sodium hydrogen exchanger in renal proximal tubules that is dependent on ketohexokinase","volume":"71","author":"Hayasaki","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"F1204","DOI":"10.1152\/ajprenal.00063.2004","article-title":"Effects of dietary fat, NaCl, and fructose on renal sodium and water transporter abundances and systemic blood pressure","volume":"287","author":"Song","year":"2004","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"F400","DOI":"10.1152\/ajprenal.00403.2014","article-title":"Sex differences in renal and metabolic responses to a high-fructose diet in mice","volume":"308","author":"Sharma","year":"2015","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"33817","DOI":"10.1074\/jbc.M700195200","article-title":"NKCC2 surface expression in mammalian cells: Down-regulation by novel interaction with aldolase B","volume":"282","author":"Benziane","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e15687","DOI":"10.14814\/phy2.15687","article-title":"Fructose-induced salt-sensitive blood pressure differentially affects sympathetically mediated aortic stiffness in male and female Sprague-Dawley rats","volume":"11","author":"Komnenov","year":"2023","journal-title":"Physiol. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bbr.2016.03.003","article-title":"Brief anesthesia by isoflurane alters plasma corticosterone levels distinctly in male and female rats: Implications for tissue collection methods","volume":"305","author":"Bekhbat","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"167","DOI":"10.33549\/physiolres.935059","article-title":"Sex differences in blood pressure, free radicals and plasma cholesterol fractions in Ren-2 transgenic rats of various ages","volume":"72","author":"Rauchova","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"245","DOI":"10.33549\/physiolres.934369","article-title":"Sex differences in blood pressure of aged Ren-2 transgenic rats","volume":"69","author":"Rauchova","year":"2020","journal-title":"Physiol. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/0023677213502015","article-title":"Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat","volume":"48","author":"Redfors","year":"2014","journal-title":"Lab. Anim."},{"key":"ref_117","first-page":"2816","article-title":"Neural regulation of renal tubular sodium reabsorption and renin secretion","volume":"44","author":"DiBona","year":"1985","journal-title":"Fed. Proc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1172\/JCI108355","article-title":"Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption","volume":"57","author":"Trevino","year":"1976","journal-title":"J. Clin. Investig."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1113\/EP085075","article-title":"Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption","volume":"100","author":"Pontes","year":"2015","journal-title":"Exp. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2147\/IBPC.S257205","article-title":"Aortic Stiffness and Diastolic Dysfunction in Sprague Dawley Rats Consuming Short-Term Fructose Plus High Salt Diet","volume":"13","author":"Komnenov","year":"2020","journal-title":"Integr. Blood Press. Control"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"F249","DOI":"10.1152\/ajprenal.00289.2023","article-title":"Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension","volume":"326","author":"Forester","year":"2024","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"F550","DOI":"10.1152\/ajprenal.00136.2018","article-title":"Fructose acutely stimulates NKCC2 activity in rat thick ascending limbs by increasing surface NKCC2 expression","volume":"316","author":"Ares","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1681\/ASN.2021121544","article-title":"Glucose\/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor","volume":"34","author":"Lee","year":"2023","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Zhang, R., Shi, S., Jadhav, D.A., Kim, N., Brostek, A., Forester, B.R., Shukla, R., Qu, C., Kramer, B., and Garvin, J.L. (2024). Abnormal activation of the mineralocorticoid receptor in the aldosterone-sensitive distal nephron contributes to fructose-induced salt-sensitive hypertension. bioRxiv.","DOI":"10.1101\/2024.08.19.608663"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00006676-198902000-00002","article-title":"Effects of mannose and fructose on the synthesis and secretion of insulin","volume":"4","author":"Curry","year":"1989","journal-title":"Pancreas"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/ajcn\/76.5.911","article-title":"Fructose, weight gain, and the insulin resistance syndrome","volume":"76","author":"Elliott","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1210\/jc.2003-031855","article-title":"Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women","volume":"89","author":"Teff","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"F577","DOI":"10.1152\/ajprenal.00240.2006","article-title":"Characterization of the regulation of renal Na+\/H+ exchanger NHE3 by insulin","volume":"292","author":"Fuster","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_129","first-page":"F265","article-title":"Insulin stimulates NaCl transport in isolated perfused MTAL of Henle\u2019s loop of rabbit kidney","volume":"267","author":"Ito","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/HJH.0b013e32835bbb83","article-title":"Insulin increases the functional activity of the renal NaCl cotransporter","volume":"31","author":"Arroyo","year":"2013","journal-title":"J. Hypertens."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Blass, G., Klemens, C.A., Brands, M.W., Palygin, O., and Staruschenko, A. (2019). Postprandial Effects on ENaC-Mediated Sodium Absorption. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40639-x"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/15\/2511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:28Z","timestamp":1760033968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/15\/2511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":131,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["nu17152511"],"URL":"https:\/\/doi.org\/10.3390\/nu17152511","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2025,7,30]]}}}