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Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes
OBJECTIVE: To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [T(mG)], increased splay, and reduced threshold), using the pancreatic/stepped hyperglyc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781504/ https://www.ncbi.nlm.nih.gov/pubmed/23735727 http://dx.doi.org/10.2337/dc13-0387 |
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author | DeFronzo, Ralph A. Hompesch, Marcus Kasichayanula, Sreeneeranj Liu, Xiaoni Hong, Ying Pfister, Marc Morrow, Linda A. Leslie, Bruce R. Boulton, David W. Ching, Agatha LaCreta, Frank P. Griffen, Steven C. |
author_facet | DeFronzo, Ralph A. Hompesch, Marcus Kasichayanula, Sreeneeranj Liu, Xiaoni Hong, Ying Pfister, Marc Morrow, Linda A. Leslie, Bruce R. Boulton, David W. Ching, Agatha LaCreta, Frank P. Griffen, Steven C. |
author_sort | DeFronzo, Ralph A. |
collection | PubMed |
description | OBJECTIVE: To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [T(mG)], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. RESEARCH DESIGN AND METHODS: Subjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5–30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves. RESULTS: At baseline, type 2 diabetic subjects had elevated T(mG), splay, and threshold compared with controls. Dapagliflozin treatment reduced the T(mG) and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects. CONCLUSIONS: The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the T(mG) and threshold at which glucose is excreted in the urine. |
format | Online Article Text |
id | pubmed-3781504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37815042014-10-01 Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes DeFronzo, Ralph A. Hompesch, Marcus Kasichayanula, Sreeneeranj Liu, Xiaoni Hong, Ying Pfister, Marc Morrow, Linda A. Leslie, Bruce R. Boulton, David W. Ching, Agatha LaCreta, Frank P. Griffen, Steven C. Diabetes Care Original Research OBJECTIVE: To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [T(mG)], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. RESEARCH DESIGN AND METHODS: Subjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5–30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves. RESULTS: At baseline, type 2 diabetic subjects had elevated T(mG), splay, and threshold compared with controls. Dapagliflozin treatment reduced the T(mG) and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects. CONCLUSIONS: The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the T(mG) and threshold at which glucose is excreted in the urine. American Diabetes Association 2013-10 2013-09-14 /pmc/articles/PMC3781504/ /pubmed/23735727 http://dx.doi.org/10.2337/dc13-0387 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research DeFronzo, Ralph A. Hompesch, Marcus Kasichayanula, Sreeneeranj Liu, Xiaoni Hong, Ying Pfister, Marc Morrow, Linda A. Leslie, Bruce R. Boulton, David W. Ching, Agatha LaCreta, Frank P. Griffen, Steven C. Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title | Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title_full | Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title_fullStr | Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title_full_unstemmed | Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title_short | Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes |
title_sort | characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781504/ https://www.ncbi.nlm.nih.gov/pubmed/23735727 http://dx.doi.org/10.2337/dc13-0387 |
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