CHRONIC SODIUM FLUORIDE INTAKE PROMOTES CHANGES IN INSULIN SIGNALING AND INFLAMMATORY PATHWAYS IN THE SKELETAL MUSCLE OF RATS

This study aimed to investigate the final step of insulin signaling and the relationship between the inflammatory pathway and insulin signal attenuation in the gastrocnemius muscle (GM) of rats chronically treated with NaF. Thirty-two seven-week-old male Wistar rats were randomly distributed into 2 groups: a control group, which was treated with drinking water without fluoride; and a fluoride group, which received drinking water with NaF and F present in their food pellets (total fluoride intake= 4.0 mg/kg body weight/day). After six weeks, the following were measured in the GM: content of protein kinase B (Akt), inhibitor of kappa B kinase (I kappa Kappa alpha/beta), tumor necrosis factora (TNF-alpha), c-Jun N-terminal kinase (JNK), and glucose transporter type 4 (GLUT4) by western blotting; phosphorylation status of Akt threonine, Akt serine, I kappa Kappa alpha/beta, and JNK by western blotting; and expression of GLUT4 mRNA by real-time PCR. The fluoridetreated rats showed a decrease (p<0.05) in the insulin-stimulated Akt serine phosphorylation status, GLUT4 gene expression and its protein content in the plasma membrane fraction and translocation index; and increased (p<0.05) I kappa Kappa alpha/beta phosphorylation status and TNF-alpha protein content in GM. No significant differences in the Akt threonine and JNK phosphorylation status, and protein contents of Akt, I kappa Kappa alpha/beta, and JNK were observed between the fluoride-treated and control rats. Chronic NaF intake led to alterations in the final step of insulin signaling, and increased the I kappa Kappa alpha/beta phosphorylation status and TNF-alpha content in GM of rats. Insulin resistance induced by excessive fluoride intake might be related to the activation of inflammatory signaling pathways.