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Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease
Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a hi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040733/ https://www.ncbi.nlm.nih.gov/pubmed/36994079 http://dx.doi.org/10.1016/j.isci.2023.106355 |
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author | Andres-Hernando, Ana Cicerchi, Christina Garcia, Gabriela E. Orlicky, David J. Stenvinkel, Peter Johnson, Richard J. Lanaspa, Miguel A. |
author_facet | Andres-Hernando, Ana Cicerchi, Christina Garcia, Gabriela E. Orlicky, David J. Stenvinkel, Peter Johnson, Richard J. Lanaspa, Miguel A. |
author_sort | Andres-Hernando, Ana |
collection | PubMed |
description | Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a high protein-based CKD model of sarcopenia in mice and differentiated human myotubes, we show that urea reduces insulin-dependent glucose and phosphate uptake by the skeletal muscle, thus contributing to the hyperphosphatemia observed in CKD whereas depleting intramuscular phosphate needed to restore energy and inhibit AMPD1. Hyperactivated AMPD1, in turn, aggravates the low energy state in the muscle by removing free adenosine monophosphate (AMP) and producing proinflammatory factors and uric acid which contribute to the progression of kidney disease. Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD. |
format | Online Article Text |
id | pubmed-10040733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100407332023-03-28 Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease Andres-Hernando, Ana Cicerchi, Christina Garcia, Gabriela E. Orlicky, David J. Stenvinkel, Peter Johnson, Richard J. Lanaspa, Miguel A. iScience Article Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a high protein-based CKD model of sarcopenia in mice and differentiated human myotubes, we show that urea reduces insulin-dependent glucose and phosphate uptake by the skeletal muscle, thus contributing to the hyperphosphatemia observed in CKD whereas depleting intramuscular phosphate needed to restore energy and inhibit AMPD1. Hyperactivated AMPD1, in turn, aggravates the low energy state in the muscle by removing free adenosine monophosphate (AMP) and producing proinflammatory factors and uric acid which contribute to the progression of kidney disease. Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD. Elsevier 2023-03-10 /pmc/articles/PMC10040733/ /pubmed/36994079 http://dx.doi.org/10.1016/j.isci.2023.106355 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Andres-Hernando, Ana Cicerchi, Christina Garcia, Gabriela E. Orlicky, David J. Stenvinkel, Peter Johnson, Richard J. Lanaspa, Miguel A. Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title | Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title_full | Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title_fullStr | Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title_full_unstemmed | Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title_short | Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease |
title_sort | phosphate depletion in insulin-insensitive skeletal muscle drives ampd activation and sarcopenia in chronic kidney disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040733/ https://www.ncbi.nlm.nih.gov/pubmed/36994079 http://dx.doi.org/10.1016/j.isci.2023.106355 |
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