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.


AIM
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.


MATERIALS AND METHODS
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.


RESULTS
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.


CONCLUSION
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.
['Malvezzi|Maria Aparecida Pereira Nunes|MAPN|', 'Pereira|Heloisa Aparecida Barbosa Silva|HABS|', 'Dionizio|Aline|A|', 'Araujo|Tamara Teodoro|TT|', 'Buzalaf|Nathalia Rabelo|NR|', 'Sabino-Arias|Isabela Tomazini|IT|', 'Fernandes|Mileni Silva|MS|', 'Grizzo|Larissa Tercilia|LT|', 'Magalhães|Ana Carolina|AC|', 'Buzalaf|Marilia Afonso Rabelo|MAR|']
D000818:Animals D001786:Blood Glucose D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D004305:Dose-Response Relationship, Drug D060766:Drinking Water D004734:Energy Metabolism D005069:Evaluation Studies as Topic D005459:Fluorides D005786:Gene Expression Regulation D005982:Glutathione Transferase D007328:Insulin D008099:Liver D051379:Mice D016688:Mice, Inbred NOD D018482:Muscle, Skeletal D040901:Proteomics D017382:Reactive Oxygen Species
Glycemia Water fluoridation Diabetes Proteomic Analysis Liver Insulinemia