This study examines the insulin response of pancreatic islets isolated from diabetic BB rats (BBD), nondiabetic BB rats (BBN), and Wistar rats to in vitro stimulation. After a 48-hour culture period, insulin release in response to glucose (17.8 mmol/L) either alone, with glucose-dependent insulinotropic polypeptide (GIP) +/- somatostatin (SS), or with Arg +/- SS was measured. A static incubation system was used. Insulin secretion from islets cultured in 4.4 mmol/L glucose (basal) did not differ between BBN and BBD rats (0.50% +/- 0.08%, 0.67% +/- 0.25% of total islet cell content [TCC], respectively). High glucose concentrations (17.8 mmol/L) stimulated a modest increase in insulin release from BBD and BBN islets (1.8% +/- 0.48% and 2.1% +/- 0.19% TCC, respectively). The addition of GIP (1 nmol/L) enhanced glucose-stimulated insulin secretion from BBN rat islets (2.9% +/- 0.42% TCC), but had no effect on BBD islets (2.04% +/- 0.57% TCC). Somatostatin (1 mumol/L) completely reversed the glucose- and/or GIP-stimulated insulin secretion from both BBN and BBD rat islets to basal levels (0.42% +/- 0.043%, 0.42% +/- 0.09% TCC, respectively). Arg (1 mmol/L) enhanced glucose-stimulated insulin secretion in both groups, although the greatest response was elicited from BBD rat islets (8.4-fold v 3.2-fold). Experiments comparing BB rats with Wistar rats demonstrated significant differences in the glucose-stimulated (17.8 mmol/L) insulin response of the islets. Islets taken from BBN and BBD were less responsive to glucose than those from Wistar rats. However, islets from BBD rats were hyperresponsive to Arg when compared with islets from Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)