Opposite effects of hypoglycemic and hyperglycemic sulfonamides upon ionophore-mediated calcium transport

Hypoglycemic sulfonylureas (gliclazide, tolbutamide) were able to mediate Li-Ca or Na-Ca countertransport in an artificial system, and enhanced A23187-mediated Ca countertransport. Diazoxide failed to cause Ca countertransport and inhibited A23187-mediated countertransport. The inhibitory effect of diazoxide was abolished by gliclazide. Comparable results were obtained when an extract of pancreatic islets was used instead of A23187 as the reference ionophoretic material. The response to hypoglycemic and/or hyperglycemic sulfonamides in the present system was qualitatively identical to their effect upon 45Ca net uptake and insulin release in intact islets. This analogy suggests that these drugs may act in the islet cells primarily by interfering with the transport of cations by native ionophores.SCOPUS: ar.j