PMID- 36279106
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230403
IS  - 1728-7731 (Electronic)
IS  - 1726-4901 (Linking)
VI  - 86
IP  - 2
DP  - 2023 Feb 1
TI  - Hypoglycemic drug liraglutide alleviates low muscle mass by inhibiting the 
      expression of MuRF1 and MAFbx in diabetic muscle atrophy.
PG  - 166-175
LID - 10.1097/JCMA.0000000000000807 [doi]
AB  - 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 (beta = 0.435, p = 0.001) and inversely 
      associated with age (beta = 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.
CI  - Copyright (c) 2022, the Chinese Medical Association.
FAU - Fan, Dongmei
AU  - Fan D
AD  - Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Department of Immunology, School of Medicine, Nankai University, Tianjin, China.
FAU - Liu, Bowei
AU  - Liu B
AD  - Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
AD  - Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, 
      China.
FAU - Yin, Fuzai
AU  - Yin F
AD  - Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
AD  - Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221024
PL  - Netherlands
TA  - J Chin Med Assoc
JT  - Journal of the Chinese Medical Association : JCMA
JID - 101174817
RN  - 0 (Hypoglycemic Agents)
RN  - 839I73S42A (Liraglutide)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - 0 (Ubiquitins)
RN  - EC 2.3.2.27 (Fbxo32 protein, mouse)
RN  - EC 2.3.2.27 (Trim63 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism
MH  - Hypoglycemic Agents/therapeutic use
MH  - *Liraglutide/therapeutic use/metabolism
MH  - Muscle, Skeletal/metabolism/pathology
MH  - Muscular Atrophy/drug therapy/chemically induced/metabolism
MH  - Peptide Hydrolases/adverse effects/metabolism
MH  - SKP Cullin F-Box Protein Ligases/metabolism/pharmacology
MH  - Ubiquitins/metabolism/pharmacology
COIS- Conflicts of interest: The authors declare that they have no conflicts of 
      interest related to the subject matter or materials discussed in this article.
EDAT- 2022/10/25 06:00
MHDA- 2023/01/21 06:00
CRDT- 2022/10/24 11:22
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2023/01/21 06:00 [medline]
PHST- 2022/10/24 11:22 [entrez]
AID - 02118582-202302000-00006 [pii]
AID - 10.1097/JCMA.0000000000000807 [doi]
PST - ppublish
SO  - J Chin Med Assoc. 2023 Feb 1;86(2):166-175. doi: 10.1097/JCMA.0000000000000807. 
      Epub 2022 Oct 24.