Effects of glipizide on the insulin production by isolated mouse pancreatic islets

Glipizide was found to stimulate the insulin release from isolated mouse pancreatic islets incubated at 5.5 mM glucose. The rate of insulin biosynthesis under similar conditions was, however, markedly depressed except at the lowest glipizide concentration tested (5 ng/ml), where the drug stimulated insulin secretion but was without effect on the biosynthetic rate. The inhibition of insulin biosynthesis was also observed in experiments with islets maintained in tissue culture, despite the fact that insulin accumulation in the culture medium was increased throughout the culture period. The present data suggest that glipizide has a transient beta-cytotropic effect, which could suggest that extra-pancreatic factors may be involved in the long-term therapeutic action of the drug.