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Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting

Currently, no ideal treatment exists to combat skeletal muscle disuse-induced atrophy and loss of strength. Because the activity of AMP-activated protein kinase (AMPK) in rat soleus muscle is suppressed at the early stages of disuse, we hypothesized that pre-treatment of rats with metformin (an AMPK...

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Autores principales: Mirzoev, Timur M., Paramonova, Inna I., Rozhkov, Sergey V., Kalashnikova, Ekaterina P., Belova, Svetlana P., Tyganov, Sergey A., Vilchinskaya, Natalia A., Shenkman, Boris S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136829/
https://www.ncbi.nlm.nih.gov/pubmed/37185725
http://dx.doi.org/10.3390/cimb45040201
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author Mirzoev, Timur M.
Paramonova, Inna I.
Rozhkov, Sergey V.
Kalashnikova, Ekaterina P.
Belova, Svetlana P.
Tyganov, Sergey A.
Vilchinskaya, Natalia A.
Shenkman, Boris S.
author_facet Mirzoev, Timur M.
Paramonova, Inna I.
Rozhkov, Sergey V.
Kalashnikova, Ekaterina P.
Belova, Svetlana P.
Tyganov, Sergey A.
Vilchinskaya, Natalia A.
Shenkman, Boris S.
author_sort Mirzoev, Timur M.
collection PubMed
description Currently, no ideal treatment exists to combat skeletal muscle disuse-induced atrophy and loss of strength. Because the activity of AMP-activated protein kinase (AMPK) in rat soleus muscle is suppressed at the early stages of disuse, we hypothesized that pre-treatment of rats with metformin (an AMPK activator) would exert beneficial effects on skeletal muscle during disuse. Muscle disuse was performed via hindlimb suspension (HS). Wistar rats were divided into four groups: (1) control (C), (2) control + metformin for 10 days (C+Met), (3) HS for 7 days (HS), (4) metformin treatment for 7 days before HS and during the first 3 days of 1-week HS (HS+Met). Anabolic and catabolic markers were assessed using WB and RT-PCR. Treatment with metformin partly prevented an HS-induced decrease in rat soleus weight and size of slow-twitch fibers. Metformin prevented HS-related slow-to-fast fiber transformation. Absolute soleus muscle force in the HS+Met group was increased vs. the HS group. GSK-3β (Ser9) phosphorylation was significantly increased in the HS+Met group vs. the HS group. Metformin pre-treatment partly prevented HS-induced decrease in 18S+28S rRNA content and attenuated upregulation of calpain-1 and ubiquitin. Thus, pre-treatment of rats with metformin can ameliorate disuse-induced reductions in soleus muscle weight, the diameter of slow-type fibers, and absolute muscle strength.
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spelling pubmed-101368292023-04-28 Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting Mirzoev, Timur M. Paramonova, Inna I. Rozhkov, Sergey V. Kalashnikova, Ekaterina P. Belova, Svetlana P. Tyganov, Sergey A. Vilchinskaya, Natalia A. Shenkman, Boris S. Curr Issues Mol Biol Article Currently, no ideal treatment exists to combat skeletal muscle disuse-induced atrophy and loss of strength. Because the activity of AMP-activated protein kinase (AMPK) in rat soleus muscle is suppressed at the early stages of disuse, we hypothesized that pre-treatment of rats with metformin (an AMPK activator) would exert beneficial effects on skeletal muscle during disuse. Muscle disuse was performed via hindlimb suspension (HS). Wistar rats were divided into four groups: (1) control (C), (2) control + metformin for 10 days (C+Met), (3) HS for 7 days (HS), (4) metformin treatment for 7 days before HS and during the first 3 days of 1-week HS (HS+Met). Anabolic and catabolic markers were assessed using WB and RT-PCR. Treatment with metformin partly prevented an HS-induced decrease in rat soleus weight and size of slow-twitch fibers. Metformin prevented HS-related slow-to-fast fiber transformation. Absolute soleus muscle force in the HS+Met group was increased vs. the HS group. GSK-3β (Ser9) phosphorylation was significantly increased in the HS+Met group vs. the HS group. Metformin pre-treatment partly prevented HS-induced decrease in 18S+28S rRNA content and attenuated upregulation of calpain-1 and ubiquitin. Thus, pre-treatment of rats with metformin can ameliorate disuse-induced reductions in soleus muscle weight, the diameter of slow-type fibers, and absolute muscle strength. MDPI 2023-04-04 /pmc/articles/PMC10136829/ /pubmed/37185725 http://dx.doi.org/10.3390/cimb45040201 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mirzoev, Timur M.
Paramonova, Inna I.
Rozhkov, Sergey V.
Kalashnikova, Ekaterina P.
Belova, Svetlana P.
Tyganov, Sergey A.
Vilchinskaya, Natalia A.
Shenkman, Boris S.
Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title_full Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title_fullStr Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title_full_unstemmed Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title_short Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
title_sort metformin pre-treatment as a means of mitigating disuse-induced rat soleus muscle wasting
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136829/
https://www.ncbi.nlm.nih.gov/pubmed/37185725
http://dx.doi.org/10.3390/cimb45040201
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