Thyroid hormone binding and deiodination by pancreatic islets: relationship with the in vitro effect upon insulin secretion

Abstract

Thyroxine dehalogenation by rat pancreatic islets was studied incubating isolated islets with labelled T4. [125I]T4 added to the incubation medium was deiodinated by the islets with the consequent production of T3, rT3 and iodide. This deiodination process showed a clear glucose-dependence, being significantly increased in the presence of 16.6 mmol/l glucose. The existence of high and low affinity binding sites for T3 was also demonstrated incubating [125I]T3 with islets under different experimental conditions. The properties of these binding sites were greatly influenced by the extracellular concentration of glucose. Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose. Our results suggest that thyroid hormones might play a direct regulatory effect on insulin secretion, probably mediated by its deiodination and interaction with specific receptors in the islet cell.