Effects of aminoguanidine on insulin release from pancreatic islets

Aminoguanidine (AG) is a potential therapeutic agent for preventing the generation of advanced glycation end products in diabetes mellitus. In this study, the effect of AG on insulin secretion was investigated in in vitro rat pancreatic islets. The islets were aseptically isolated and cultured in tissue culture medium 199 for 48 h with or without AG. After the culture, batches of 10 islets were incubated in Krebs-Ringer bicarbonate buffer containing 3.3 mM or 16.7 mM glucose. Islets previously exposed to 0.18 mM AG or 0.45 mM AG showed similar insulin release to control islets at a 16.7 mM glucose concentration, but high glucose-stimulated insulin release was inhibited in the islets exposed to 1.8 mM. In the perifusion experiment, insulin release caused by 16.7 mM glucose from the islets previously exposed to 1.8 mM AG was not significantly different from that of the control islets. However, culture of the islets with higher AG concentrations, 4.55 mM and 9.1 mM, significantly inhibited glucose-stimulated insulin release (< 0.02 and 0.002, respectively). These results suggest that AG at high concentrations impairs pancreatic B-cell response to a high concentration of glucose.