Time-dependent effect of GABA on glucose-stimulated insulin secretion from isolated islets in rat

Objective. Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter found widely in the central nervous system and some peripheral tissues such as the islets of pancreas. The aim of this study was to determine the time dependency of the effect of GABA on glucose-stimulated insulin secretion in isolated islets of rats. Materials and Methods. The collagenase digestion technique was used to isolate the islets from pancreata of male Wistar rats (200-250 g). Insulin secretion was assessed in islets exposed to different concentrations of glucose (8.3 and 16.7 mM), in the presence or absence of GABA (50 mu M), for different incubation times and also pre-incubation of islets with GABA, 30 and 45 min before 8.3 mM glucose stimulation. Furthermore insulin secretion with different concentrations of glucose (8.3 and 16.7 mM), and in the presence or absence of different concentrations of baclofen, a GABA(B) agonist and of saclofen, a GABA(B) antagonist during 1 h of incubation was assessed. Insulin release was reported as mean +/- SE mu U/islet/min and p values of <0.05 were considered significant. Results. GABA with concentration of 50 mu M inhibited the glucose stimulated insulin secretion during a 60 min incubation period. Baclofen had no significant effect on glucose-induced insulin secretion, while saclofen (100 mu M) significantly increased 16.7 mM glucose-induced insulin secretion in 60 min of incubation (p < 0.05). Pre-incubation of islets with GABA for 45 min, before glucose stimulation, increased glucose-induced insulin secretion. Conclusion. GABA could have both stimulatory and inhibitory effects on glucose-stimulated insulin secretion, depending on the time of exposure and glucose concentration.