Publisher：東京医学社  

DOI： 10.24479/kd.0000001506

CiNii Research

Language：English   Publisher：Journal of Cachexia, Sarcopenia and Muscle  

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.

DOI： 10.1002/jcsm.13350

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Biochemical Journal  

There has been a concern that sodium-glucose cotransporter 2 (SGLT2) inhibitors could reduce skeletal muscle mass and function. Here, we examine the effect of canagliflozin (CANA), an SGLT2 inhibitor, on slow and fast muscles from nondiabetic C57BL/6J mice. In this study, mice were fed with or without CANA under ad libitum feeding, and then evaluated for metabolic valuables as well as slow and fast muscle mass and function. We also examined the effect of CANA on gene expressions and metabolites in slow and fast muscles. During SGLT2 inhibition, fast muscle function is increased, as accompanied by increased food intake, whereas slow muscle function is unaffected, although slow and fast muscle mass is maintained. When the amount of food in CANA-treated mice is adjusted to that in vehicle-treated mice, fast muscle mass and function are reduced, but slow muscle was unaffected during SGLT2 inhibition. In metabolome analysis, glycolytic metabolites and ATP are increased in fast muscle, whereas glycolytic metabolites are reduced but ATP is maintained in slow muscle during SGLT2 inhibition. Amino acids and free fatty acids are increased in slow muscle, but unchanged in fast muscle during SGLT2 inhibition. The metabolic effects on slow and fast muscles are exaggerated when food intake is restricted. This study demonstrates the differential effects of an SGLT2 inhibitor on slow and fast muscles independent of impaired glucose metabolism, thereby providing new insights into how they should be used in patients with diabetes, who are at a high risk of sarcopenia.

DOI： 10.1042/BCJ20210700

Scopus

PubMed

Event date： 2021.10

Language：Japanese  

Venue：沖縄   Country：Japan  

Event date： 2020.10 - 2019.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大津市   Country：Japan  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese   Publisher：(一社)日本クリニカルパス学会  

Language：Japanese   Publisher：(公財)日本糖尿病財団  

Language：Japanese   Publisher：(株)羊土社  

本邦における肥満・2型糖尿病を代表とする生活習慣病の罹患率は増加の一途を辿り、大きな社会問題となっている。生活習慣病の発症と進展には遺伝因子が重要であるが、栄養・代謝などの環境因子がエピゲノム変化としてゲノム上に記憶され、疾患の発症・進展に影響することが報告されている。栄養素の代謝過程で生じる中間代謝産物は情報伝達分子としてエピゲノム修飾に関わるが、栄養・代謝によるエピゲノム修飾・遺伝子発現制御の分子機序の解明によりエピゲノムを臨床応用した先制医療の実践が期待される。(著者抄録)

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

現代社会において肥満やそれに伴う糖尿病、脂質異常症、心血管疾患などの合併症は急増しており、大きな社会問題となっている。生活習慣病は患者自身が疾患に対する正しい知識を持ち、積極的に治療に取り組む必要がある一方で、多くの情報が氾濫し誤った生活習慣を実践している場合も多い。本市民公開講座では客観的なエビデンスに基づいた正しい知識を市民に分かりやすく、興味を持たれるように説明し、実践的な医学的知識、食事療法への取り組み、生活習慣の改善に伴うストレスにいかに対処していくかについての講演を中心に行った。

Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

現代社会において肥満やそれに伴う糖尿病、脂質異常症、心血管疾患などの合併症は急増しており、大きな社会問題となっている。生活習慣病は患者自身が疾患に対する正しい知識を持ち、積極的に治療に取り組む必要がある一方で、多くの情報が氾濫し誤った生活習慣を実践している場合も多い。本市民公開講座では客観的なエビデンスに基づいた正しい知識を市民に分かりやすく、興味を持たれるように説明し、実践的な医学的知識、食事療法への取り組み、生活習慣の改善に伴うストレスにいかに対処していくかについての講演を中心に行った。