Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus

Autor: Shintaro Nakamura, Yasutaka Miyachi, Akihito Shinjo, Hisashi Yokomizo, Masatomo Takahashi, Kohta Nakatani, Yoshihiro Izumi, Hiroko Otsuka, Naoichi Sato, Ryuichi Sakamoto, Takashi Miyazawa, Takeshi Bamba, Yoshihiro Ogawa
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 14, Iss 6, Pp 2866-2881 (2023)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13350
Popis: Abstract Background Diabetes is associated with an increased risk of deleterious changes in muscle mass and function or sarcopenia, leading to physical inactivity and worsening glycaemic control. Given the negative energy balance during sodium–glucose cotransporter‐2 (SGLT2) inhibition, whether SGLT2 inhibitors affect skeletal muscle mass and function is a matter of concern. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains insufficiently explored. We aimed to explore the effects of canagliflozin (CANA), an SGLT2 inhibitor, on skeletal muscles in genetically diabetic db/db mice focusing on the differential responses of oxidative and glycolytic muscles. Methods Db/db mice were treated with CANA for 4 weeks. We measured running distance and handgrip strength to assess skeletal muscle function during CANA treatment. At the end of the experiment, we performed a targeted metabolome analysis of the skeletal muscles. Results CANA treatment improved the reduced endurance capacity, as revealed by running distance in db/db mice (414.9 ± 52.8 vs. 88.7 ± 22.7 m, P
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