Metformin attenuates the TLR4 inflammatory pathway in skeletal muscle of diabetic rats

• Published in: Acta diabetologica 2017-10, Vol.54 (10), p.943-951
• Main Authors: Peixoto, Leonardo Gomes, Teixeira, Renata Roland, Vilela, Danielle Diniz, Barbosa, Lara Naves, Caixeta, Douglas Carvalho, Deconte, Simone Ramos, de Assis de Araújo, Fernanda, Sabino-Silva, Robinson, Espindola, Foued Salmen
• Format: Article
• Language: English
• Subjects: Animals; Antidiabetics; Chemokine CXCL1 - genetics; Chemokine CXCL1 - immunology; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - immunology; Enzyme-linked immunosorbent assay; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Inflammation; Insulin; Insulin Resistance; Internal Medicine; JNK protein; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metformin; Metformin - administration & dosage; Muscle, Skeletal - drug effects; Muscle, Skeletal - immunology; Musculoskeletal system; NF-kappa B - genetics; NF-kappa B - immunology; Original Article; Pharmacology; Rats; Rats, Wistar; Rodents; Signal transduction; Signal Transduction - drug effects; Skeletal muscle; Soleus muscle; TLR2 protein; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Western blotting
• ISSN: 0940-5429; 1432-5233
• DOI: 10.1007/s00592-017-1027-5

Aims Inflammation induced by hyperglycemia triggers the toll-like receptor (TLR) pathway into cells. Our hypothesis was that metformin treatment attenuates the TLR signaling pathways triggered by inflammation in skeletal muscle of hypoinsulinemic/hyperglycemic STZ-induced rats. Thus, we examined TLR signaling under hypoinsulinemia and hyperglycemia conditions and its correlation with insulin resistance in muscle of diabetic rats treated with metformin. Methods Ten-day diabetic rats were submitted to 7 days of saline ( D group) or metformin (500 mg/kg once per day) ( D  +  M group). The skeletal muscle was collected before the insulin tolerance test. Then, Western blotting analysis of skeletal muscle supernatant was probed with TLR4, TLR2, NF-κB, IκB, p-AMPK and p-JNK. TNF-α and CXCL1/KC content was analyzed by ELISA. Results Metformin treatment increased whole-body insulin sensitivity. This regulation was accompanied by a parallel change of p-AMPK and by an inverse regulation of TLR4 and NF-κB contents in the soleus muscle ( r  = 0.7229, r  = −0.8344 and r  = −0.7289, respectively, Pearson correlation; p