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

Autor: Simone Ramos Deconte, Renata Roland Teixeira, Fernanda de Assis Araújo, Lara Naves Barbosa, Danielle Diniz Vilela, Douglas Carvalho Caixeta, Robinson Sabino-Silva, Foued Salmen Espindola, Leonardo Gomes Peixoto
Rok vydání: 2017
Předmět:
Zdroj: Acta Diabetologica. 54:943-951
ISSN: 1432-5233
0940-5429
Popis: 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. 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. 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
Databáze: OpenAIRE