Effects of Chronic Fluoride Exposure on the Duodenum of Diabetic Mice

Objectives: Diabetes mellitus is currently considered a disease of great impact, with type 2 diabetes (T2D) having the highest prevalence. Some studies have indicated that excessive fluoride (F) intake causes insulin resistance, an initial effect in the development of T2D. Gastrointestinal symptoms are the first signs of toxicity by F. In this work, diabetic mice chronically exposed to F had the duodenum evaluated by proteomics analysis.
Methods: 18 male C57BL/6J mice were divided into 3 groups (n=6/group) according to the F dosage administered in drinking water (0, 10 or 50 mgF/L). They received hyperlipidic diet until they weighed 30 g. Control animals received normocaloric diet and water containing 0 mgF/L for the same period. After reaching the established weight, the animals received daily intraperitoneal injections of streptozotocin (SZT), for 3 days. The animals had their blood glucose measured weekly and were considered diabetic when it reached 200 mg/dL. After the experimental period, the animals were euthanized and the duodenum was collected for proteomic analysis. Control animals showed a significant decrease in blood glucose when compared to the groups that received hyperlipidic diet. After 3 weeks of application of SZT and installation of T2D, the groups received treatments with or without F.
Results: As a result, a significant reduction in blood glucose was observed in animals that consumed F-containing water (10 and 50 mgF/L) in comparison to those receiving 0 mgF/L and controls. The proteomic analysis of the duodenum showed changes in the abundance of several proteins correlated with important biological processes, such as protein synthesis, glucose homeostasis and energy metabolism.
Conclusions: These data indicate that the administration of F during the second week significantly reduced the glycemia of the animals after the installation of T2D and provide new insights into the mechanisms involved in the F toxicity in the gut.