Abstract: | Summary 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 -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 -ketobutyrate all substances which were effective in reversing the inhibition of D-glucose-induced insulin release were glycolytic intermediates. Comparing the glycolytic -ketoacid pyruvate and the non-glycolytic ketoacid -ketobutyrate, the only part common to both substances was the ketoacid moiety. It is concluded from these findings that the ketoacid moiety of the -ketoacids plays an important role in reversing the effect of thyroxine on D-glucose-induced insulin release.This work was presented in part at the 11th Annual Meeting of the European Association for the Study of Diabetes, Munich, September, 1975 |