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 |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty endocrine system diseases Chemokine CXCL1 Endocrinology Diabetes and Metabolism Inflammation Diabetes Mellitus Experimental 03 medical and health sciences Endocrinology Insulin resistance Diabetes mellitus Internal medicine Internal Medicine medicine Animals Humans Hypoglycemic Agents Rats Wistar Muscle Skeletal Soleus muscle Tumor Necrosis Factor-alpha business.industry Insulin tolerance test NF-kappa B nutritional and metabolic diseases Skeletal muscle General Medicine medicine.disease Metformin Rats Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure TLR4 Insulin Resistance medicine.symptom business Signal Transduction medicine.drug |
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 |
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