Liraglutide ameliorates diabetic lung injury and muscle damage via `TLR4/NF-κB` and `Atrogin-1/AMPK` pathway modulation.

Beyond traditional metabolic disturbances, Type 2 Diabetes (T2DM) is increasingly recognized for causing end-organ damage, including under-recognized pulmonary and skeletal muscle dysfunction. Current standard-of-care primarily targets glycemic control, often falling short in preventing these broader complications. This study investigates whether liraglutide, a GLP-1 receptor agonist known for its metabolic benefits, can offer protective effects against these specific non-metabolic impairments, addressing a critical gap in comprehensive diabetes management.

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 using methods such as ELISA and Western blot. In skeletal muscle, MAPK and HSP70 levels, and Atrogin-1 and AMPK expression were evaluated. Histopathological changes were examined in both tissues to assess structural integrity and damage.

Diabetic rats exhibited significant hyperglycemia, dyslipidemia, and elevated methylglyoxal and HIF-1α levels, indicating systemic metabolic dysfunction and hypoxia. In the lung, markers of oxidative stress and inflammation were significantly increased, specifically elevated IL-1β levels and enhanced expression of NF-κB and TLR4, key mediators of inflammatory responses. Skeletal muscle in diabetic rats showed a clear increase in muscle atrophy, reflected by altered expression of MAPK and HSP70 levels, and dysregulation of Atrogin-1 (a muscle-specific ubiquitin ligase involved in atrophy) and AMPK (a critical energy sensor).