Abstract
Several new non-sulfonylurea hypoglycemic agents such as A-4166, KAD-1229 and repaglinide
are structurally related to meglitinide, previously known as the non-sulfonylurea
moiety of glibenclamide, or its analog S 3075. There is no parallelism between the
ionophoretic and insulinotropic efficiency of these compounds. They are all able,
however, to decrease K+ conductance in islet cells as documented by a decrease in 86Rb outflow from prelabelled pancreatic islets. In terms of concentrations of equal
insulinotropic capacity, a difference of at least two orders of magnitude is observed
between the weakest (meglitinide) and most potent (S 3075) compound. All these agents
exert little effect upon insulin release in nutrient-deprived islets, but markedly
augment glucose-stimulated insulin release. The hexose can be replaced, however, by
a non-glucidic nutrient such as the methyl ester of succinic acid to support the insulinotropic
action of the meglitinide analogs. The question is raised as to the potential advantage
of these non-sulfonylurea insulinotropic agents over hypoglycemic sulfonylureas.
Key words
Meglitinide - A-4166 - KAD-1229 - Repaglinide - S 3075
