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Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development
The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintainin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763788/ https://www.ncbi.nlm.nih.gov/pubmed/33190567 http://dx.doi.org/10.1161/JAHA.120.018889 |
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author | Gronda, Edoardo Jessup, Mariell Iacoviello, Massimo Palazzuoli, Alberto Napoli, Claudio |
author_facet | Gronda, Edoardo Jessup, Mariell Iacoviello, Massimo Palazzuoli, Alberto Napoli, Claudio |
author_sort | Gronda, Edoardo |
collection | PubMed |
description | The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective. |
format | Online Article Text |
id | pubmed-7763788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77637882020-12-28 Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development Gronda, Edoardo Jessup, Mariell Iacoviello, Massimo Palazzuoli, Alberto Napoli, Claudio J Am Heart Assoc Contemporary Review The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective. John Wiley and Sons Inc. 2020-11-14 /pmc/articles/PMC7763788/ /pubmed/33190567 http://dx.doi.org/10.1161/JAHA.120.018889 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Contemporary Review Gronda, Edoardo Jessup, Mariell Iacoviello, Massimo Palazzuoli, Alberto Napoli, Claudio Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title | Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title_full | Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title_fullStr | Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title_full_unstemmed | Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title_short | Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development |
title_sort | glucose metabolism in the kidney: neurohormonal activation and heart failure development |
topic | Contemporary Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763788/ https://www.ncbi.nlm.nih.gov/pubmed/33190567 http://dx.doi.org/10.1161/JAHA.120.018889 |
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