Glucose-dependency of bradykinin-induced insulin secretion from the perfused rat pancreas

In order to investigate the glucose dependency of bradykinin (BK)-induced insulin secretion, rat pancreata were perfused in situ with BK (1 microM) for 30 min in the presence of glucose concentrations of 0 - 20 mM. Glucose (6 mM) alone maintained a steady baseline insulin secretion which was 6.7 %/- 0.5 ng/min (n = 4). The rate of insulin secretion in the presence of 0 and 1 mM glucose was approximately 70 - 80% and approximately 60-70% less, respectively, than in the presence of 6 mM glucose. The perfusate glucose concentrations of 10 and 20 mM induced a biphasic and dose-dependent insulin secretion, characterized by a transient increase followed by a sustained phase; the sustained phase was higher than the transient increase. BK failed to change insulin secretion in the absence of extracellular glucose. When BK was administered in 1 mM glucose, it induced a transient insulin release peak which was 2.8-fold of the insulin secretion induced by 6 mM glucose, then the insulin concentrations of the effluents decreased gradually to the levels that were slightly higher than that induced by the 1 mM glucose alone, but lower than that induced by 6 mM glucose. After BK was administered in 6 mM glucose, it induced a transient insulin release peak that was 3.6-fold of the baseline level, and followed by a sustained insulin secretion phase which was approximately 50% higher than that of the 6 mM glucose control group. When BK was perfused with 10 or 20mM glucose, it induced a similar insulin secretion pattern as in the glucose alone groups. However, the combination of glucose (10 or 20 mM) and BK induced a higher transient insulin release peak, which was 7.8- and 12-fold of the baseline level, respectively. Also, the BK-glucose-induced sustained phase was higher than the transient peak. BK caused a greater potentiation of insulin secretion in 20 mM glucose than in 10 mM glucose. Taken together, our findings suggest that 1) BK requires the presence of glucose to stimulate insulin secretion and 2) BK induces insulin secretion in a glucose concentration-dependent manner; the higher the glucose concentration, the greater the potentiation in BK-induced insulin secretion.