Effects of exercise, metformin, and combination treatments on type 2 diabetic mellitus-induced muscle atrophy in db/db mice: Crosstalk between autophagy and the proteasome
J. physiol. biochem
; 80(1): 235-247, Feb. 2024. ilus, graf
Article
in En
| IBECS
| ID: ibc-229953
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
Both exercise and metformin are common effective clinical treatments of type 2 diabetic mellitus. This study investigated the functional role of exercise, metformin, and combination treatment on type 2 diabetic mellitusinduced muscle atrophy. In this experiment, a total of 10 BKS mice were set as the control group. A total of 40 BKS-db/db mice were randomly divided into the control group (db/db); the exercise intervention group (db/db + Ex), which ran on a treadmill at 712 m/min, 3040 min/day, 5 days/week; the metformin administration group (db/db + Met), which was administered 300 mg/kg of metformin solution by gavage daily; and the exercise combined with metformin administration group (db/db + Ex + Met). After 8 weeks of intervention, their tibialis anterior muscles were removed. The levels of insulin signaling pathway proteins, ubiquitin proteasome, and autophagic lysosomeassociated proteins were detected using western blot, the expression of MuRF1 and Atrogin-1 was detected using immunohistochemical staining, and the degradation of autophagosomes was detected using double-labeled immunofluorescence. The db/db mice exhibited reduced insulin sensitivity and inhibition of the autophagiclysosome system, the ubiquitinproteasome system was activated, and protein degradation was exacerbated, leading to skeletal muscle atrophy. Exercise and metformin and their combined interventions can increase insulin sensitivity, whereas exercise alone showed more effective in inhibiting the ubiquitinproteasome system, improving autophagy levels, and alleviating skeletal muscle atrophy. Compared with metformin, exercise demonstrated superior improvement of muscle atrophy by promoting the synthesis and degradation of autophagy through the AMPK/ULK1 pathway. However, the combination treatment exhibits no synergistic effect on muscle atrophy. (AU)
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Collection:
06-national
/
ES
Database:
IBECS
Main subject:
Autophagy
/
Muscular Atrophy
/
Exercise
/
Diabetes Mellitus, Type 2
/
Proteasome Inhibitors
/
Metformin
Limits:
Animals
Language:
En
Journal:
J. physiol. biochem
Year:
2024
Document type:
Article