Published in:
01-10-2017 | Original Article
Metformin attenuates the TLR4 inflammatory pathway in skeletal muscle of diabetic rats
Authors:
Leonardo Gomes Peixoto, Renata Roland Teixeira, Danielle Diniz Vilela, Lara Naves Barbosa, Douglas Carvalho Caixeta, Simone Ramos Deconte, Fernanda de Assis de Araújo, Robinson Sabino-Silva, Foued Salmen Espindola
Published in:
Acta Diabetologica
|
Issue 10/2017
Login to get access
Abstract
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 < 0.05). Metformin treatment increased IκB content when compared to D rats. In addition, metformin treatment decreased p-JNK independently of TLR2 signal in diabetic rats.
Conclusion
In summary, the results indicate a relationship between muscular TLR4, p-AMPK and NF-κB content and insulin sensitivity. The study also highlights that in situations of insulin resistance, such as in diabetic subjects, metformin treatment may prevent attenuation of activation of the inflammatory pathway.