Low-level fluoride exposure reduces glycemia in NOD mice

Water fluoridation is the most widespread measure to prevent dental caries but its relationship with the development of type-1 diabetes (T1D), which has been increasing by 2-5% worldwide, is not quite well understood.

This study evaluated if fluoride (F) administered in the drinking water can prevent or reduce the development of T1D in non-obese diabetic (NOD) mice, as well as to explore the underlying mechanisms.

Twenty-four weaning NOD mice received water containing 0, 10 or 50 ppm F for 21 days. Plasma glucose and insulin were analyzed. Quantitative proteomic analysis was conducted in the liver and gastrocnemius muscle.

Animals treated with 10 ppm F had significantly lower glucose levels than the control group, but there was no significant difference among the groups in relation to insulin. The % of β-cell function was significantly higher in the 10 ppm F group. Changes in the proteomic profile of muscle and liver were seen among the groups. In the muscle, the 10 ppm F group presented, when compared with control, increased expression of proteins involved in energy metabolism. The 50 ppm F group, compared with control, presented increased expression of proteins related to muscle contraction, differentiation of brown adipose tissue and apoptosis. For the liver, the 10 ppm F group had increase in proteins involved in energy metabolism and protein synthesis, in respect to control. There was also an increase in isoforms of Glutathione S transferase, which was confirmed by Western blotting. In the group treated with 50 ppm F, proteins related to ROS metabolism and energetic metabolism were altered.

Increased expression of antioxidant proteins by treatment with low F concentration may possibly help to explain protection against the development of T1D, which should be better explored in future mechanistic studies.