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Effect of fluoride on the secretion of insulin in the rat

Inés Menoyo1, Alfredo Rigalli, Rodolfo C Puche

  • 1Laboratorio de Biología Osea, Facultad de Ciencias Médicas, Rosario, Argentina.

Arzneimittel-Forschung
|September 10, 2005
PubMed

Insights

Sodium fluoride (5-20 micromol/L) inhibits glucose-stimulated insulin secretion from Langerhans islets and rat pancreatic tissue. This effect is rapidly reversible and occurs downstream of key signaling pathways.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Toxicology

Background:

  • Insulin secretion is a complex process regulated by various intracellular signaling pathways.
  • The role of extracellular ions, such as fluoride, in modulating insulin release is not fully understood.

Purpose of the Study:

  • To investigate the effect of sodium fluoride on insulin secretion from pancreatic islets.
  • To determine the specific stage of the insulin secretion pathway affected by fluoride.

Main Methods:

  • Isolated rat Langerhans islets were used to study insulin secretion in vitro.
  • Rat pancreatic tissue was perfused in vivo to assess the effects of fluoride on insulin release.
  • The impact of fluoride on insulin secretion stimulated by glucose, ionophore A23187, phorbol-ester, and forskolin was examined.

Main Results:

  • Sodium fluoride (5-20 micromol/L) significantly inhibited glucose-stimulated insulin secretion in isolated islets and perfused pancreatic tissue.
  • Fluoride reduced both initial and sustained phases of insulin secretion in vivo.
  • The inhibitory effects of various secretagogues, including ionophore A23187, phorbol-ester, and forskolin, were blunted by fluoride.

Conclusions:

  • Fluoride interferes with a critical step in insulin secretion occurring downstream of calmodulin, protein-kinase C, and cyclic AMP.
  • The findings suggest that fluoride acts at a late stage in the insulin secretion cascade.
  • The rapid reversibility of the inhibition indicates a dynamic interaction between fluoride and the secretory machinery.

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