Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume
Abstract Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stab...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.14360 |
| _version_ | 1818291463066222592 |
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| author | Takahiro Masuda Shigeaki Muto Keiko Fukuda Minami Watanabe Ken Ohara Hermann Koepsell Volker Vallon Daisuke Nagata |
| author_facet | Takahiro Masuda Shigeaki Muto Keiko Fukuda Minami Watanabe Ken Ohara Hermann Koepsell Volker Vallon Daisuke Nagata |
| author_sort | Takahiro Masuda |
| collection | DOAJ |
| description | Abstract Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto‐Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24‐hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute‐free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin‐treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin‐induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV. |
| first_indexed | 2024-12-13T02:44:28Z |
| format | Article |
| id | doaj.art-7f897b7c175e45e0a5eefad60dc7a9bc |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-13T02:44:28Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-7f897b7c175e45e0a5eefad60dc7a9bc2022-12-22T00:02:13ZengWileyPhysiological Reports2051-817X2020-01-0182n/an/a10.14814/phy2.14360Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volumeTakahiro Masuda0Shigeaki Muto1Keiko Fukuda2Minami Watanabe3Ken Ohara4Hermann Koepsell5Volker Vallon6Daisuke Nagata7Division of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanDivision of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanDivision of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanDivision of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanDivision of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanDepartment of Molecular Plant Physiology and Biophysics Julius‐von‐Sachs‐Institute of BiosciencesUniversity of Würzburg Würzburg Bavaria GermanyDivision of Nephrology and Hypertension Department of Medicine and Pharmacology University of California San Diego &VA San Diego Healthcare System San Diego CA USADivision of Nephrology Department of Internal Medicine Jichi Medical University Shimotsuke Tochigi JapanAbstract Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto‐Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24‐hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute‐free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin‐treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin‐induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.https://doi.org/10.14814/phy2.14360bioimpedance analysisglucosuriaSGLT2 inhibitionvasopressinwater reabsorption |
| spellingShingle | Takahiro Masuda Shigeaki Muto Keiko Fukuda Minami Watanabe Ken Ohara Hermann Koepsell Volker Vallon Daisuke Nagata Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume Physiological Reports bioimpedance analysis glucosuria SGLT2 inhibition vasopressin water reabsorption |
| title | Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume |
| title_full | Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume |
| title_fullStr | Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume |
| title_full_unstemmed | Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume |
| title_short | Osmotic diuresis by SGLT2 inhibition stimulates vasopressin‐induced water reabsorption to maintain body fluid volume |
| title_sort | osmotic diuresis by sglt2 inhibition stimulates vasopressin induced water reabsorption to maintain body fluid volume |
| topic | bioimpedance analysis glucosuria SGLT2 inhibition vasopressin water reabsorption |
| url | https://doi.org/10.14814/phy2.14360 |
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