Comparison in Rabbits of Hypoglycemia and B Cell Degranulation After Various Sulfonylureas. ∗

Abstract

Summary

1) A single injection of same dose of 3 sulfonylureas, tolbutamide, chlorpropamide and metahexamide showed that tolbutamide caused a lesser hypoglycemia, whereas the 2 other drugs caused a more severe lowering of blood sugar level, most marked after administration of chlorpropamide. In no case was any B cell degranulation observed. 2) Infusion of glucose alone or simultaneously with various drugs for 7 hours each day on 3 successive days caused an identical hyperglycemic response in all animals. However, infusion of glucose alone produced no B cell degranulation; when sulfonylureas were added to the perfusate, degranulation of B cells was found. This was most pronounced after administration of chlorpropamide and metahexamide. That absence of hypoglycemia did not prevent B cell degranulation is further proof that degranulation of B cells after sulfonylureas is a primary action of these drugs on B cells to increase insulin output. Furthermore, relative B cell degranulating efficacy of the 3 compounds, in accord with their hypoglycemic effectiveness, supports the conclusion that they act directly on the B cell.