Different Pharmacological Properties of GLUT9a and GLUT9b: Potential Implications in Preeclampsia

Lüscher, Benjamin P.; Surbek, Daniel; Clémençon, Benjamin; Huang, Xiao; Albrecht, Christiane; Marini, Camilla; Hediger, Matthias A.; Baumann, Marc

doi:10.33594/000000154

Cited by 8 publications

(7 citation statements)

References 36 publications

(41 reference statements)

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“…This might be attributed to the bioactive contents which were initially too low in concentration to yield any effects, but later became effective once the dosage increased. Even though both of these splice variants, GLUT9a and GLUT9b, have identical roles in urate kinetics, a recent study showed that the former has higher sensitivity against small anions [ 37 ]. Nonetheless, it is still unclear how the expressions were modulated in this present study.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid-Rich Extract from Holothuria atra for Hyperuricemia via Expressions Modulation of GLUT9a and GLUT9b in Rat Model

et al. 2023

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An edible sea cucumber Holothuria atra has been hypothesized to have medicinal benefits against hyperuricemia owing to its bioactive compounds, including mono- and poly-unsaturated fatty acids. Herein, we aimed to investigate the fatty acids-rich extract produced from H. atra to treat hyperuricemic rats (Rattus novergicus). The extraction was carried out using n-hexane solvent and then administered to potassium oxonate-induced hyperuricemic rats, with allopurinol acting as a positive control. The extract (50, 100, 150 mg/kg body weight) and allopurinol (10 mg/kg) were administered QD through an oral route using a nasogastric tube. Serum uric acid, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and blood urea nitrogen of the abdominal aortic blood were investigated. Our results suggested that the extract was rich in polyunsaturated (arachidonic acid) and monounsaturated fatty acids (oleic acid), in which its administration of 150 mg/kg could significantly reduce serum uric acid (p < 0.001), AST (p = 0.001), and ALT (p = 0.0302). The anti-hyperuricemic activity could be associated with the modulation of GLUT9 by the H. atra extract. In conclusion, the n-hexane extract from H. atra is a potential serum uric acid-lowering agent targeting GLUT9, where further investigations are crucially warranted.

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Section: Discussionmentioning

confidence: 99%

Fatty Acid-Rich Extract from Holothuria atra for Hyperuricemia via Expressions Modulation of GLUT9a and GLUT9b in Rat Model

et al. 2023

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“…GLUT9 protein is expressed in two subtypes, namely, GLUT9a and GLUT9b, localized in the apical and basolateral membrane of the proximal tubule, respectively. GLUT9 subtypes regulate uric acid transportation and concentration [ 85 ]. Chino et al revealed that the urinary excretion rate of uric acid strongly correlated with the urinary glucose excretion, demonstrating the relation between SUA and glycosuria [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis

Akbari

Rafiee

Sathyapalan

et al. 2022

Journal of Diabetes Research

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Background. Several trials have assessed the antihyperglycemic effects of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the impact of SGLT2is on serum uric acid (SUA) in patients with T2DM. Methods. Placebo-controlled trials published before 13 August 2021 were identified by searching PubMed, Embase, Web of Science, and Scopus. The intervention group received SGLT2i as monotherapy or add-on treatment, and the control group received a placebo that was replaced with SGLT2i. Clinical trials providing changes in SUA were included. The mean change of SUA, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were calculated (PROSPERO CRD42021287019). Results. After screening of 1172 papers, 59 papers were included in the systematic review. A total of 55 trials (122 groups) of 7 types of SGLT2i on patients with T2DM were eligible for meta-analysis. All SGLT2is significantly decreased SUA levels compared with the placebo groups: empagliflozin mean difference MD = − 40.98 μmol/L, 95% CI [-47.63, -34.32], dapagliflozin MD = − 35.17 μmol/L, 95% CI [-39.68, -30.66], canagliflozin MD = − 36.27 μmol/L, 95% CI [−41.62, −30.93], luseogliflozin MD = − 24.269 μmol/L, 95% CI [-33.31, -15.22], tofogliflozin MD = − 19.47 μmol/L, 95% CI [−27.40, −11.55], and ipragliflozin MD = − 18.85 μmol/L, 95% CI [−27.20, −10.49]. SGLT2i also decreased FPG, body weight, and HbA1c levels. SUA reduction persisted during long-term treatment with SGLT2i (except for empagliflozin), while the SUA reduction was affected by the duration of diabetes. Conclusions. SGLT2i can be a valid therapeutic strategy for patients with T2DM and comorbid hyperuricemia. Besides reducing FPG, body weight, and HbA1c, SGLT2i can significantly decrease SUA levels compared to placebo (Total MD = − 34.07 μmol/L, 95% CI [-37.00, -31.14]).

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“…The simultaneous presence of GLUT9a and GLUT9b in the microvillus (apical) membrane of syncytiotrophoblasts may facilitate uric acid transportation from the fetoplacental unit into the maternal circulation, which is crucial for fetal well-being and survival. Our group has previously demonstrated that, in contrast to GLUT9b, GLUT9a is regulated by iodine [ 21 ]. The question of whether the localization of placental GLUT9a, i.e., on the microvillus membrane, is important for the regulation of transplacental uric acid transport capacity remains to be solved.…”

Section: Discussionmentioning

confidence: 99%

Glucose Transporter 9 (GLUT9) Plays an Important Role in the Placental Uric Acid Transport System

Lüscher

Albrecht

Stieger

et al. 2022

Cells

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Background: Hyperuricemia is a common laboratory finding in pregnant women compromised by preeclampsia. A growing body of evidence suggests that uric acid is involved in the pathogenesis of preeclampsia. Glucose transporter 9 (GLUT9) is a high-capacity uric acid transporter. The aim of this study was to investigate the placental uric transport system, and to identify the (sub-) cellular localization of GLUT9. Methods: Specific antibodies against GLUT9a and GLUT9b isoforms were raised, and human villous (placental) tissue was immunohistochemically stained. A systemic GLUT9 knockout (G9KO) mouse model was used to assess the placental uric acid transport capacity by measurements of uric acid serum levels in the fetal and maternal circulation. Results: GLUT9a and GLUT9b co-localized with the villous (apical) membrane, but not with the basal membrane, of the syncytiotrophoblast. Fetal and maternal uric acid serum levels were closely correlated. G9KO fetuses showed substantially higher uric acid serum concentrations than their mothers. Conclusions: These findings demonstrate that the placenta efficiently maintains uric acid homeostasis, and that GLUT9 plays a key role in the placental uric acid transport system, at least in this murine model. Further studies investigating the role of the placental uric acid transport system in preeclampsia are eagerly needed.

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Different Pharmacological Properties of GLUT9a and GLUT9b: Potential Implications in Preeclampsia

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 8 publications

References 36 publications

Fatty Acid-Rich Extract from Holothuria atra for Hyperuricemia via Expressions Modulation of GLUT9a and GLUT9b in Rat Model

Fatty Acid-Rich Extract from Holothuria atra for Hyperuricemia via Expressions Modulation of GLUT9a and GLUT9b in Rat Model

Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis

Glucose Transporter 9 (GLUT9) Plays an Important Role in the Placental Uric Acid Transport System

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