The inhibition of insulin secretion from the perfused rat pancreas after thyroxine treatment.

Thyroxine treatment did not significantly affect the immediate insulin secretory response of the perfused rat pancreas, but it inhibited the late phase of D-glucose-induced insulin secretion. Thyroxine treatment did not inhibit D-glyceraldehyde-, D-mannose-, and tolbutamide-induced insulin release from the perfused pancreas. An increase in the D-glucose concentration of the perfusion medium as well as feeding of the rats did not restore insulin secretion after thyroxine treatment. The inhibition of D-glucose-induced insulin release in response to thyroxine treatment was reversed after addition of either D-glyceraldehyde, dihydroxyacetone, DL-glyceric acid, pyruvate, or alpha-ketobutyrate to the perfusion medium. Tolbutamide, L-glucose, D-fructose, D-mannose, L-lactate, and propionic acid were not able to overcome the inhibition of D-glucose-induced insulin secretion. Except for alpha-ketobutyrate all substances which were effective in reversing the inhibition of D-glucose-induced insulin release were glycolytic intermediates. Comparing the glycolytic alpha-ketoacid pyruvate and the non-glycolytic ketoacid alpha-ketobutyrate, the only part common to both substances was the ketoacid moiety. It is concluded from these findings that the ketoacid moiety of the alpha-ketoacids plays an important role in reversing the effect of thyroxine on D-glucose-induced insulin release.