Impaired fatigue resistance, sarcoplasmic reticulum function, and mitochondrial activity in soleus muscle of db/db mice

Abstract Type 2 diabetes mellitus (T2DM) is characterized by reduced exercise tolerance due to increased fatigability in skeletal muscle. In this study, we investigated muscle fatigue resistance of soleus (SOL) muscle in obese type 2 diabetic model mice (db/db). No differences in muscle volume, abso...

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Bibliographic Details
Main Authors: Hiro Yamamoto, Hiroaki Eshima, Saori Kakehi, Ryuzo Kawamori, Hirotaka Watada, Yoshifumi Tamura
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:Physiological Reports
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Online Access:https://doi.org/10.14814/phy2.15478
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Summary:Abstract Type 2 diabetes mellitus (T2DM) is characterized by reduced exercise tolerance due to increased fatigability in skeletal muscle. In this study, we investigated muscle fatigue resistance of soleus (SOL) muscle in obese type 2 diabetic model mice (db/db). No differences in muscle volume, absolute force, or specific force in SOL muscle were observed between db/db mice and control mice (db/+), while fatigue resistance evaluated by repeated tetanic contractions was significantly lower in db/db mice (30th tetani, db/+: 63.7 ± 4.7%, db/db: 51.3 ± 4.8%). The protein abundance related to Ca2+ release from the sarcoplasmic reticulum (SR) in SOL muscle was not different between db/db mice and db/+ mice, while SR Ca2+‐ATPase (Ca2+ reuptake to SR) protein was decreased in db/db mice compared to db/+ mice (db/+: 1.00 ± 0.17, db/db: 0.60 ± 0.04, relative units). In addition, mitochondrial oxidative enzyme activity (succinate dehydrogenase) was decreased in the SOL muscle of db/db mice (p < 0.05). These data suggest that fatigue resistance in slow‐twitch dominant muscle is impaired in mice with T2DM. Decreased mitochondrial oxidative enzyme activity and impairment of Ca2+ uptake to SR, or both might be involved in the mechanisms.
ISSN:2051-817X