Effect of fluoride on parameters related to glucose homeostasis: unraveling mechanisms

• Grant number: 20/04369-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2021
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Marília Afonso Rabelo Buzalaf
• Grantee: Juliana Sanches Trevizol
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated scholarship(s): 24/07452-9 - Acute exposure to Fluorotelomer alcohol (FTOH) and fluoride via Free Fatty Acid Receptor 1 (GPR40) in Beta cells, BE.EP.DR

Abstract

Water fluoridation is an important public health measure for the control of dental caries. Animal studies from our group have shown that low doses of Fluoride (F) in the drinking water, similar to those found in public water supplies, increase insulin sensitivity and reduce blood glucose in diabetic rodents. Recently, we observed that NOD mice exposed to low doses of F present a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. This led us to propose that the reduction in PEPCK, a positive regulator of gluconeogenesis, leads to increased glucose uptake, which could be a probable mechanism to explain the anti-diabetic effects of low doses of F. The present proof-of-concept study was designed to shed light into this mechanism. We will employ in vitro (AM-12 hepatic cells) and in vivo (NOD mice) models to explore the relationship between exposure to low F levels, nuclear enolase and cytoplasmic PEPCK. The results to be obtained are important for public health, as the fluoridation of public water supply, in addition to controlling tooth decay, can also play an important role in Diabetes therapy. (AU)