Low-level fluoride exposure reduces glycemia in NOD mice

Ecotoxicol Environ Saf. 2019 Jan 30;168:198-204. doi: 10.1016/j.ecoenv.2018.10.055. Epub 2018 Oct 30.


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.

Keywords: Diabetes; Glycemia; Insulinemia; Liver; Proteomic Analysis; Water fluoridation.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / prevention & control
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Dose-Response Relationship, Drug
  • Drinking Water
  • Energy Metabolism
  • Evaluation Studies as Topic
  • Fluorides / blood
  • Fluorides / pharmacology*
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • Insulin / blood
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred NOD
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Proteomics
  • Reactive Oxygen Species / metabolism


  • Blood Glucose
  • Drinking Water
  • Insulin
  • Reactive Oxygen Species
  • Glutathione Transferase
  • Fluorides