Immunoreactive insulin (IRI) and C-peptide secretory responses to consecutive stimulations with terbutaline, glucagon, glucose and a standard meal were investigated in fasted subjects with newly diagnosed, untreated Type 2 diabetes with and without concomitant administration of the sulphonylurea agent glipizide (5 mg). Basal concentrations of blood glucose were 8.7 +/- 0.8 mmol/l without glipizide, and 6.6 +/- 0.5 mmol/l with glipizide (p less than 0.01). This difference in prestimulation glucose levels persisted throughout the study. It was found that glipizide potentiated the IRI and C-peptide secretion in response to terbutaline (125 micrograms i.v.). The absolute IRI and C-peptide secretory responses to glucagon (250 micrograms i.v.) were of similar magnitudes with or without glipizide, despite the lower blood glucose concentrations after glipizide. Allowing for the lower blood glucose, IRI and C-peptide responses to glucagon were potentiated by glipizide. Glucose (6 g i.v.) exerted no IRI or C-peptide secretory effect in these patients either without or with glipizide. The changes in blood glucose concentration after injection of glucagon were not altered by glipizide. On the contrary, the terbutaline-induced increment in blood glucose concentration was inhibited by glipizide and the glucose elimination rate after glucose injection was slightly enhanced by glipizide; effects explained by the higher plasma insulin levels. After meal ingestion, the absolute IRI and C-peptide secretory responses were slightly enhanced by glipizide. Glipizide had no effect on the meal-induced changes in blood glucose concentrations. In conclusion, glipizide had the ability to cause an absolute potentiation of beta 2-adrenoceptor-stimulated and meal-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)