Liraglutide ameliorates diabetic lung injury and muscle damage via modulation of TLR4/NF-κB and Atrogin-1/AMPK signaling pathways.

BACKGROUND: Diabetic complications extend beyond metabolic disturbances to include end-organ damage, with emerging evidence including lung and skeletal muscle dysfunction as under recognized manifestations. This study investigated the protective effects of liraglutide against pulmonary and muscular impairments in a rat model of type 2 diabetes. METHODS: Fifteen rats were divided into three groups: control, diabetic, and diabetic treated with liraglutide. Serum parameters including fasting blood glucose (FBG), HbA1c, lipid profile, methylglyoxal, and hypoxia-inducible factor-1α (HIF-1α) were assessed. In lung tissue, IL-1β levels and NF-κB and TLR4 expression were analyzed. In skeletal muscle, MAPK and HSP70 levels, and Atrogin-1 and AMPK expression were evaluated. Histopathological changes were examined in both tissues. RESULTS: Diabetic rats exhibited significant hyperglycemia, dyslipidemia, elevated methylglyoxal and HIF-1α, along with increased oxidative stress and inflammation in the lung, while skeletal muscle showed an increase of muscle atrophy. Liraglutide treatment significantly ameliorated molecular and structural alterations in both organs. CONCLUSION: Liraglutide exerts protective effects against diabetic lung injury and skeletal muscle damage by attenuating oxidative stress, inflammation, and atrophy-related signaling pathways.