Hypoglycemic drug liraglutide alleviates low muscle mass by inhibiting the expression of MuRF1 and MAFbx in diabetic muscle atrophy

Abstract

Background: Low muscle mass, that is, muscular atrophy, is an independent risk factor for type 2 diabetes mellitus (T2DM). Few studies investigated whether hypoglycemic drugs can alleviate low muscle mass and related mechanisms. Methods: This study recruited 51 type 2 diabetes mellitus (T2DM) patients, who were divided into two groups based on skeletal muscle index (SMI) evaluated by Dual-energy X-ray absorptiometry (DXA): the experiment group (n = 25, SMI < 7 kg/m 2 ) and the control group (n = 26, SMI≥7 kg/m 2 ). GLP-1 levels were measured by ELISA. In vitro, 10 KK-A y mice (11-to 12-week-old) were assigned into two groups: liraglutide group (n = 5) and saline group (n = 5). Real-time PCR and Western blot were used to determine the expression levels of muscle specific ubiquitin protease E3, MuRF1, and MAFbx. Results: T2DM patients with a higher SMI had significantly higher GLP-1 levels (t = 3.77, p < 0.001). SMI were positively associated with GLP-1 levels (β = 0.435, p = 0.001) and inversely associated with age (β = 0.299, p = 0.015). The incidence of low muscle mass at below the second quartiles was 10.55 times that of above the second quartiles (odds ratio = 10.556, p < 0.001). Liraglutide-treatment mice showed significant decrease in food intake, final body weight, fasting blood glucose, and significant increase in skeletal muscle mass, which coincided with the significant decrease in the expression levels of ubiquitin protease E3 MuRF1 and MAFbx. In vitro studies showed that liraglutide promoted myogenic differentiation and attenuated dexamethasone (DEX)-induced myotube atrophy. Ectopic expression of MuRF1 and MAFbx antagonized the beneficial effects of liraglutide on DEX-induced myotube atrophy. Conclusion: T2DM patients have muscular atrophy, and liraglutide alleviates muscular atrophy at least in part by inhibiting the expression of MuRF1 and MAFbx.

Uncovering the potential molecular mechanism of liraglutide to alleviate the effects of high glucose on myoblasts based on high-throughput transcriptome sequencing technique

“…MAFbx and MuRF1 also play important regulatory roles in skeletal muscle atrophy and muscle injury [ 20 ]. Moreover, a study showed that liraglutide can alleviate low muscle mass by inhibiting the expression of MAFbx and MuRF1 in patients with diabetic muscle atrophy [ 21 ]. Western blot results showed that high glucose promoted the expression of MAFbx and MuRF1 in C2C12 myoblasts, and liraglutide could inhibit this phenomenon.…”

Connecting the dots: Sarcopenia’s roles on chronic condition management toward healthy aging

“…14 Besides, people with type 2 diabetes mellitus and lower skeletal muscle mass have lower glucagon-like peptide-1 levels, and treatment with liraglutide can alleviate muscle atrophy, which could have implications for muscle health in aging. 15 Among hopes for curative chronic disease therapies, caring for patients' quality of life through improving strength, function, and participation remains paramount. This requires recognizing sarcopenia not as an inevitable consequence, but as a critical target for intervention.…”

“…14 Besides, people with type 2 diabetes mellitus and lower skeletal muscle mass have lower glucagon-like peptide-1 levels, and treatment with liraglutide can alleviate muscle atrophy, which could have implications for muscle health in aging. 15…”

The Landscape of Accessible Chromatin and Developmental Transcriptome Maps Reveal a Genetic Mechanism of Skeletal Muscle Development in Pigs

“…The domestic pig ( Sus scrofa ) is one of the main protein sources utilized by humans and an excellent research model for human muscle-related diseases [ 1 , 2 ]. The association between muscle insulin resistance and mitochondrial dysfunction is a common feature in the elderly and people who are susceptible to or have dominant type 2 diabetes mellitus [ 3 , 4 ]. The skeletal muscle is mainly composed of connective tissue and muscle fibers, which have the ability to regenerate and self-repair after injury [ 5 , 6 ].…”