Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus
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 SGLT...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.13350 |
| _version_ | 1797375110598885376 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shintaro Nakamura |
| collection | DOAJ |
| description | 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 < 0.05). Targeted metabolome analysis revealed that 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranosyl 5′‐monophosphate (AICARP), a naturally occurring AMP‐activated protein kinase (AMPK) activator, increased in the oxidative soleus muscle (P < 0.05), but not in the glycolytic extensor digitorum longus muscle (P = 0.4376), with increased levels of AMPK phosphorylation (P < 0.01). Conclusions This study highlights the potential role of the AICARP/AMPK pathway in oxidative rather than glycolytic skeletal muscles during SGLT2 inhibition, providing novel insights into the mechanism by which SGLT2 inhibitors improve endurance capacity in patients with type 2 diabetes. |
| first_indexed | 2024-03-08T19:17:29Z |
| format | Article |
| id | doaj.art-66ebd4fd133149fc8dbed7cb49027203 |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-03-08T19:17:29Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-66ebd4fd133149fc8dbed7cb490272032023-12-27T05:05:03ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092023-12-011462866288110.1002/jcsm.13350Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleusShintaro Nakamura0Yasutaka Miyachi1Akihito Shinjo2Hisashi Yokomizo3Masatomo Takahashi4Kohta Nakatani5Yoshihiro Izumi6Hiroko Otsuka7Naoichi Sato8Ryuichi Sakamoto9Takashi Miyazawa10Takeshi Bamba11Yoshihiro Ogawa12Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation Kyushu University Fukuoka JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanAbstract 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 < 0.05). Targeted metabolome analysis revealed that 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranosyl 5′‐monophosphate (AICARP), a naturally occurring AMP‐activated protein kinase (AMPK) activator, increased in the oxidative soleus muscle (P < 0.05), but not in the glycolytic extensor digitorum longus muscle (P = 0.4376), with increased levels of AMPK phosphorylation (P < 0.01). Conclusions This study highlights the potential role of the AICARP/AMPK pathway in oxidative rather than glycolytic skeletal muscles during SGLT2 inhibition, providing novel insights into the mechanism by which SGLT2 inhibitors improve endurance capacity in patients with type 2 diabetes.https://doi.org/10.1002/jcsm.13350AICARPAMPKendurance exercisefatty acid oxidationSGLT2 inhibitorskeletal muscle |
| spellingShingle | 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 Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus Journal of Cachexia, Sarcopenia and Muscle AICARP AMPK endurance exercise fatty acid oxidation SGLT2 inhibitor skeletal muscle |
| title | Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus |
| title_full | Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus |
| title_fullStr | Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus |
| title_full_unstemmed | Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus |
| title_short | Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus |
| title_sort | improved endurance capacity of diabetic mice during sglt2 inhibition role of aicarp an ampk activator in the soleus |
| topic | AICARP AMPK endurance exercise fatty acid oxidation SGLT2 inhibitor skeletal muscle |
| url | https://doi.org/10.1002/jcsm.13350 |
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