Effect of GLP-1 receptor agonist, liraglutide, on muscle in spontaneously diabetic torii fatty rats
Abstract
This study investigated the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on skeletal muscles in rats with type 2 diabetes. Male SDT fatty rats (8-week-old) were provided liraglutide, or insulin-hydralazine for 8 weeks; control SDT fatty rats and SD rats were administered a vehicle. At 16 weeks of age, muscle strength of limbs was significantly lower in all SDT fatty rats compared to SD rats. While cross-sectional areas of type IIb muscle fibers in extensor digitorum longus muscle were significantly lower in SDT fatty rats than in SD rats, those of type I muscle fibers in soleus were similar in all rats. In the soleus of SDT fatty rats, liraglutide led to greater citrate synthase activity and cytochrome c oxidase subunit 5 B protein expression, independently of blood glucose and blood pressure levels. Liraglutide may contribute to preservation of mitochondrial content on soleus muscle in type 2 diabetes.
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Yamada et al. found that increasing doses of liraglutide over 6 weeks increased protein expression of Cox5B (subunit of Complex V) compared with control SDT fatty rats.
“They found that increasing doses of liraglutide over 6 weeks increased protein expression of Cox5B (subunit of Complex V) when compared with the control SDT fatty rats [37].”
From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [37]
Yamada et al. found a strong trend for an increase in citrate synthase activity in the soleus muscle (p=0.05) but no effect in the EDL.
“There was also a strong trend for an increase in citrate synthase activity (SDT untreated vs. SDT + liraglutide p = 0.05) in the soleus muscle, but no effect was seen in the EDL.”
From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [37]
This positive effect was not consistent; there is unclear and conflicting evidence on mitochondrial mass and PGC-1α, effects upon which appear sensitive to the particular muscle measured.
“However, this was not a consistent finding, and we do present some unclear and conflicting evidence on mitochondrial mass and PGC‐1α, effects upon which appear to be sensitive to the particular muscle measured [37].”
From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [37]
Yamada et al. found no significance in PGC-1α protein expression following liraglutide in the soleus muscle between control SD mice and SDT mice treated with liraglutide, but there was significantly higher expression of PGC-1α in the EDL muscle.
“However, Yamada and colleagues found no significance in PGC‐1α protein expression following liraglutide in the soleus muscle between the control SD mice and the SDT mice treated with liraglutide, but there was a significantly higher expression of PGC‐1α in the extensor digitorum longus (EDL) muscle [37].”
From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [37]
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- Authors
- Yamada, S., Ogura, Y., Inoue, K., Tanabe, J., Sugaya, T., Ohata, K., Nagai, Y., Natsuki, Y., Hoshino, S., Watanabe, S., Ichikawa, D., Kimura, K., Shibagaki, Y., & Kamijo-Ikemori, A.
- Affiliations
- St. Marianna University School of Medicine (JP)
- Japan Community Healthcare Organization (JP)
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 539
- Pages
- 111472
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W3203398030
- Cited by
- 25
- References
- 27
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (JP 19K11478)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- liraglutide, GLP-1 receptor agonists, type 2 diabetes, skeletal muscle, muscle strength, type IIb muscle fibers, type I muscle fibers, extensor digitorum longus, soleus muscle, mitochondrial content, citrate synthase, muscle fiber cross-sectional area
- MeSH terms
- Liraglutide, Animals, Citrate (si)-Synthase, Electron Transport Complex IV, Diabetes Mellitus, Type 2, Gene Expression Regulation, Hydralazine, Insulin, Male, Obesity, Comorbidity, Rats, Sprague-Dawley, Muscle, Skeletal, Rats, Muscle Strength
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